[Intoxication of botulinum toxin].

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Chudzicka, Aleksandra

2015-09-01

Botulinum toxin is an egzotoxin produced by Gram positive bacteria Clostridium botulinum. It is among the most potent toxins known. The 3 main clinical presentations of botulism are as follows: foodborne botulism, infant botulism and wound botulism. The main symptom of intoxication is flat muscles paralysis. The treatment is supportive care and administration of antitoxin. In prevention the correct preparing of canned food is most important. Botulinum toxin is accepted as a biological weapon. © 2015 MEDPRESS.

Crystallization and preliminary X-ray analysis of a novel haemagglutinin component of the toxin complex of serotype C Clostridium botulinum.

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Hayashi, Shintaro; Akiyama, Tomonori; Sagane, Yoshimasa; Miyashita, Shin-Ichiro; Watanabe, Toshihiro; Yajima, Shunsuke; Niwa, Koichi

2014-03-01

The botulinum toxin complex, the causative agent of botulism, passes through the intestinal wall via sugar-chain-dependent cell binding of a haemagglutinin of 33 kDa molecular weight (HA-33). The amino-acid sequence of the C-terminal half of HA-33 of the serotype C strain Yoichi (C-Yoichi) shares only 46% identity with those of the major serotype C strains. Additionally, C-Yoichi HA-33 exhibits a unique sugar-binding specificity. In the present work, C-Yoichi HA-33 was expressed in Escherichia coli and crystallized. Diffraction data were collected at a resolution of 2.2 Å. The crystals belonged to space group R3. The complete detailed protein structure will yield insight into how the unique HA-33 protein recognizes sugar moieties.

Evaluation of a quail embryo model for the detection of botulinum toxin type A activity

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The quail embryo was evaluated for use as a bioassay to detect biologically active botulinum toxin serotype A (BoNT/A). Day 15 of incubation embryos were injected with decreasing dosages of BoNT/A from 250 to 0.5 ng of toxin. At 1 day post-injection, embryos receiving 20 ng of BoNT or higher had m...

Role of Botulinum Toxin in Depression.

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Parsaik, Ajay K; Mascarenhas, Sonia S; Hashmi, Aqeel; Prokop, Larry J; John, Vineeth; Okusaga, Olaoluwa; Singh, Balwinder

2016-03-01

The goal of this review was to consolidate the evidence concerning the efficacy of botulinum toxin type A (onabotulinumtoxinA) in depression. We searched MEDLINE, EMBASE, Cochrane, and Scopus through May 5, 2014, for studies evaluating the efficacy of botulinum toxin A in depression. Only randomized controlled trials were included in the meta-analysis. A pooled mean difference in primary depression score, and pooled odds ratio for response and remission rate with 95% confidence interval (CI) were estimated using the random-effects model. Heterogeneity was assessed using Cochran Q test and χ statistic. Of the 639 articles that were initially retrieved, 5 studies enrolling 194 subjects (age 49±9.6 y) were included in the systematic review, and 3 randomized controlled trials enrolling 134 subjects were included in the meta-analysis. The meta-analysis showed a significant decrease in mean primary depression scores among patients who received botulinum toxin A compared with placebo (-9.80; 95% CI, -12.90 to -6.69) with modest heterogeneity between the studies (Cochran Q test, χ=70). Response and remission rates were 8.3 and 4.6 times higher, respectively, among patients receiving botulinum toxin A compared with placebo, with no heterogeneity between the studies. The 2 studies excluded from the meta-analysis also found a significant decrease in primary depression scores in patients after receiving botulinum toxin A. A few subjects had minor side effects, which were similar between the groups receiving botulinum toxin and those receiving placebo. This study suggests that botulinum toxin A can produce significant improvement in depressive symptoms and is a safe adjunctive treatment for patients receiving pharmacotherapy for depression. Future trials are needed to evaluate the antidepressant effect per se of botulinum toxin A and to further elucidate the underlying antidepressant mechanism of botulinum toxin A.

Botulinum toxin: yesterday, today, tomorrow

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A. R. Artemenko

2013-01-01

Full Text Available Botulinum toxin (BoNT is a bacterial neurotoxin presented with seven serotypes that inhibit neurotransmitter release from nerve endings. The serotypes of BoNT are antigenically dissimilar, act via different, but interconnected mechanisms, and are not interchangeable. The activity of BoNT is associated with impaired neuroexocytosis occurring in several steps: from the binding of BoNT to its specific receptor on the axon terminal membrane to the proteolytic enzymatic cleavage of SNARE substrate. The effect of BoNT is considered to be restricted to the peripheral nervous system, but when given in particularly high doses, it has been recently shown to affect individual brain structures. In addition, by modulating peripheral afferentation, BoNT may influence the excitability of central neuronal structures at both spinal and cortical levels. Only BoNT serotypes A and B are used in clinical practice and aesthetic medicine. The type A has gained the widest acceptance as a therapeutic agent for more than 100 abnormalities manifesting themselves as muscular hyperactivity, hyperfunction of endocrine gland, and chronic pain. The effect of BoNT preparations shows itself 2-5 days after injection, lasts 3 months or more, and gradually decreases with as a result of pharmacokinetic and intracellular reparative processes. Biotechnology advances and potentialities allow purposefully modification of the protein molecular structure of BoNT, which expands the use and efficiency of performed therapy with neurotoxins. Recombinant technologies provide a combination of major therapeutic properties of each used BoNT serotype and expand indications for recombinant chimeric toxins.

Botulinum Toxin: Pharmacology and Therapeutic Roles in Pain States.

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Patil, Shilpadevi; Willett, Olga; Thompkins, Terin; Hermann, Robert; Ramanathan, Sathish; Cornett, Elyse M; Fox, Charles J; Kaye, Alan David

2016-03-01

Botulinum toxin, also known as Botox, is produced by Clostridium botulinum, a gram-positive anaerobic bacterium, and botulinum toxin injections are among the most commonly practiced cosmetic procedures in the USA. Although botulinum toxin is typically associated with cosmetic procedures, it can be used to treat a variety of other conditions, including pain. Botulinum toxin blocks the release of acetylcholine from nerve endings to paralyze muscles and to decrease the pain response. Botulinum toxin has a long duration of action, lasting up to 5 months after initial treatment which makes it an excellent treatment for chronic pain patients. This manuscript will outline in detail why botulinum toxin is used as a successful treatment for pain in multiple conditions as well as outline the risks associated with using botulinum toxin in certain individuals. As of today, the only FDA-approved chronic condition that botulinum toxin can be used to treat is migraines and this is related to its ability to decrease muscle tension and increase muscle relaxation. Contraindications to botulinum toxin treatments are limited to a hypersensitivity to the toxin or an infection at the site of injection, and there are no known drug interactions with botulinum toxin. Botulinum toxin is an advantageous and effective alternative pain treatment and a therapy to consider for those that do not respond to opioid treatment. In summary, botulinum toxin is a relatively safe and effective treatment for individuals with certain pain conditions, including migraines. More research is warranted to elucidate chronic and long-term implications of botulinum toxin treatment as well as effects in pregnant, elderly, and adolescent patients.

Botulinum toxin in trigeminal neuralgia.

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Castillo-Álvarez, Federico; Hernando de la Bárcena, Ignacio; Marzo-Sola, María Eugenia

2017-01-06

Trigeminal neuralgia is one of the most disabling facial pain syndromes, with a significant impact on patients' quality of life. Pharmacotherapy is the first choice for treatment but cases of drug resistance often require new strategies, among which various interventional treatments have been used. In recent years a new therapeutic strategy consisting of botulinum toxin has emerged, with promising results. We reviewed clinical cases and case series, open-label studies and randomized clinical trials examining the use of botulinum toxin for drug-refractory trigeminal neuralgia published in the literature. The administration of botulinum toxin has proven to be a safe and effective therapeutic strategy in patients with drug-refractory idiopathic trigeminal neuralgia, but many questions remain unanswered as to the precise role of botulinum toxin in the treatment of this disease. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

USE OF BOTULINUM TOXIN TYPE A IN THE TREATMENT OF SPASTICITY IN CHILDREN WITH CEREBRAL PALSY

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Ljiljana Lazić

2011-06-01

Full Text Available Cerebral palsy has an incidence of about 1-2 per 1000 live births, and in spite of the progress of neonatal medicine, it seems that the incidence will not subside in the near future. The most important characteristic of cerebral palsy is movement abnormality: spasticity, chorea, athetosis, ataxia, dystonia, as well as their different combinations. About 70% of children who suffer from cerebral palsy also suffer from some form of spasticity. Spasticity is a type of muscle hypertonicity characterized by rapid increase in resistance to passive stretching of muscles. The interest for botulinum toxin application in the treatment of spasticity has dramatically increased in the last 10 years. Botulinum toxin is the most powerful neurotoxin that is found in nature. It is produced by anaerobic bacteria – clostridium botulinum. It is produced in eight serotypes of which type A is the most commonly used. Botulinum toxin blocks neuromuscular transmission and causes irreversible weakness of the treated muscle. It has been used since 1993 in the treatment of cerebral palsy in children. The toxin effect is permanent and it results in irreversible denervation. Functional recovery is possible after 2-4 months, due to sprouting of nerve endings and the formation of new synaptic contacts. Treatment with botulinum toxin is safe. Adverse effects are rare, temporary and completely reversible. Application of botulinum toxin prevents or reduces contractures and deformities, and thus delays or avoids surgical treatment. Yet, physical therapy, which prolongs and improves the effects of botulinum toxin, remains an essential and most important form of therapy in the treatment of children with cerebral palsy.

Botulinum toxin for the treatment of strabismus.

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Rowe, Fiona J; Noonan, Carmel P

2017-03-02

The use of botulinum toxin as an investigative and treatment modality for strabismus is well reported in the medical literature. However, it is unclear how effective it is in comparison to other treatment options for strabismus. The primary objective was to examine the efficacy of botulinum toxin therapy in the treatment of strabismus compared with alternative conservative or surgical treatment options. This review sought to ascertain those types of strabismus that particularly benefit from the use of botulinum toxin as a treatment option (such as small angle strabismus or strabismus with binocular potential, i.e. the potential to use both eyes together as a pair). The secondary objectives were to investigate the dose effect and complication rates associated with botulinum toxin. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to July 2016), Embase (January 1980 to July 2016), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to July 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 July 2016. We handsearched the British and Irish Orthoptic Journal, Australian Orthoptic Journal, proceedings of the European Strabismological Association (ESA), International Strabismological Association (ISA) and International Orthoptic Association (IOA) (www.liv.ac.uk/orthoptics/research/search.htm) and American Academy of Paediatric Ophthalmology and Strabismus meetings (AAPOS). We contacted researchers who are active in this field for information about further

Botulinum toxin for the treatment of bruxism.

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Tinastepe, Neslihan; Küçük, Burcu Bal; Oral, Koray

2015-10-01

Botulinum toxin, the most potent biological toxin, has been shown to be effective for a variety of disorders in several medical conditions, when used both therapeutically and cosmetically. In recent years, there has been a rising trend in the use of this pharmacological agent to control bruxing activity, despite its reported adverse effects. The aim of this review was to provide a brief overview to clarify the underlying essential ideas for the use of botulinum toxin in bruxism based on available scientific papers. An electronic literature search was performed to identify publications related to botulinum toxin and its use for bruxism in PubMed. Hand searching of relevant articles was also made to identify additional studies. Of the eleven identified studies, only two were randomized controlled trials, compared with the effectiveness of botulinum toxins on the reduction in the frequency of bruxism events and myofascial pain after injection. The authors of these studies concluded that botulinum toxin could be used as an effective treatment for reducing nocturnal bruxism and myofascial pain in patients with bruxism. Evidence-based research was limited on this topic. More randomized controlled studies are needed to confirm that botulinum toxin is safe and reliable for routine clinical use in bruxism.

Botulinum toxin for vaginismus treatment.

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Ferreira, Juliana Rocha; Souza, Renan Pedra

2012-01-01

Vaginismus is characterized by recurrent or persistent involuntary contraction of the perineal muscles surrounding the outer third of the vagina when penile, finger, tampon, or speculum penetration is attempted. Recent results have suggested the use of botulinum toxin for the treatment of vaginismus. Here, we assessed previously published data to evaluate the therapeutic effectiveness of botulinum toxin for vaginismus. We have carried out a systematic review followed by a meta-analysis. Our results indicate that botulinum toxin is an effective therapeutic option for patients with vaginismus (pooled odds ratio of 8.723 with 95% confidence interval limits of 1.942 and 39.162, p = 0.005). This may hold particularly true in treatment-refractory patients because most of the studies included in this meta-analysis have enrolled these subjects in their primary analysis. Botulinum toxin appears to bea reasonable intervention for vaginismus. However, this conclusion should be read carefully because of the deficiency of placebo-controlled randomized clinical trials and the quality issues presented in the existing ones.

Llama Single Domain Antibodies Specific for the 7 Botulinum Neurotoxin Serotypes as Heptaplex Immunoreagents

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Collazo, M. Thelma; Garza, John A.; Hayhurst, Andrew

2010-01-01

Background There are currently 7 known serotypes of botulinum neurotoxin (BoNT) classified upon non-cross reactivity of neutralizing immunoglobulins. Non-neutralizing immunoglobulins, however, can exhibit cross-reactivities between 2 or more serotypes, particularly mosaic forms, which can hamper the development of highly specific immunoassays, especially if based on polyclonal antisera. Here we employ facile recombinant antibody technology to subtractively select ligands to each of the 7 BoNT serotypes, resulting in populations with very high specificity for their intended serotype. Methods and Findings A single llama was immunized with a cocktail of 7 BoNT toxoids to generate a phage display library of single domain antibodies (sdAb, VHH or nanobodies) which were selected on live toxins. Resulting sdAb were capable of detecting both toxin and toxin complex with the best combinations able to detect 100s-10s of pg per 50 µL sample in a liquid bead array. The most sensitive sdAb were combined in a heptaplex assay to identify each of the BoNT serotypes in buffer and milk and to a lesser extent in carrot juice, orange juice and cola. Several anti-A(1) sdAb recognized A2 complex, showing that subtype cross-reactivity within a serotype was evident. Many of our sdAb could act as both captor and tracer for several toxin and toxin complexes suggesting sdAb can be used as architectural probes to indicate BoNT oligomerisation. Six of 14 anti-A clones exhibited inhibition of SNAP-25 cleavage in the neuro-2A assay indicating some sdAb had toxin neutralizing capabilities. Many sdAb were also shown to be refoldable after exposure to high temperatures in contrast to polyclonal antisera, as monitored by circular dichroism. Conclusions Our panel of molecularly flexible antibodies should not only serve as a good starting point for ruggedizing assays and inhibitors, but enable the intricate architectures of BoNT toxins and complexes to be probed more extensively. PMID:20098614

Report of Allergic Reaction After Application of Botulinum Toxin.

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Careta, Mariana Figueiroa; Delgado, Livia; Patriota, Régia

2015-07-01

Botulinum toxin is a widely used treatment with satisfactory results, and it is relatively safe in the doses used for cosmetic procedures. The authors report a case of allergic reaction to Chinese botulinum toxin serotype A (CBTX-A). Although this is a rare adverse event, it is nonetheless clinically relevant to healthcare professionals. A 44-year-old woman presented to the authors' hospital complaining of dynamic wrinkles. CBTX-A was used to treat her. Minutes after application, she developed urticarial plaques proximal to the injection site. The patient had an allergic reaction, as documented by a positive skin test, which was controlled by the administration of antihistamines and systemic corticosteroids. This report is intended to guide healthcare professionals faced with this type of adverse event regarding how to proceed without hindering the delivery and effectiveness of the treatment. When performed by a qualified health professional, this treatment brings excellent results in the vast majority of cases. 5 Risk. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

Botulinum toxin in pain treatment.

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Colhado, Orlando Carlos Gomes; Boeing, Marcelo; Ortega, Luciano Bornia

2009-01-01

Botulinum toxin (BTX) is one of the most potent bacterial toxins known and its effectiveness in the treatment of some pain syndromes is well known. However, the efficacy of some of its indications is still in the process of being confirmed. The objective of this study was to review the history, pharmacological properties, and clinical applications of BTX in the treatment of pain of different origins. Botulinum toxin is produced by fermentation of Clostridium botulinum, a Gram-positive, anaerobic bacterium. Commercially, BTX comes in two presentations, types A and B. Botulinum toxin, a neurotoxin with high affinity for cholinergic synapses, blocks the release of acetylcholine by nerve endings without interfering with neuronal conduction of electrical signals or synthesis and storage of acetylcholine. It has been proven that BTX can selectively weaken painful muscles, interrupting the spasm-pain cycle. Several studies have demonstrated the efficacy and safety of BTX-A in the treatment of tension headaches, migraines, chronic lumbar pain, and myofascial pain. Botulinum toxin type A is well tolerated in the treatment of chronic pain disorders in which pharmacotherapy regimens can cause side effects. The reduction in the consumption of analgesics and length of action of 3 to 4 months per dose represent other advantages of its use. However, further studies are necessary to establish the efficacy of BTX-A in chronic pain disorders and its exact mechanism of action, as well as its potential in multifactorial treatments.

Botulinum Toxin for Rhinitis.

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Ozcan, Cengiz; Ismi, Onur

2016-08-01

Rhinitis is a common clinical entity. Besides nasal obstruction, itching, and sneezing, one of the most important symptoms of rhinitis is nasal hypersecretion produced by nasal glands and exudate from the nasal vascular bed. Allergic rhinitis is an IgE-mediated inflammatory reaction of nasal mucosa after exposure to environmental allergens. Idiopathic rhinitis describes rhinitis symptoms that occur after non-allergic, noninfectious irritants. Specific allergen avoidance, topical nasal decongestants, nasal corticosteroids, immunotherapy, and sinonasal surgery are the main treatment options. Because the current treatment modalities are not enough for reducing rhinorrhea in some patients, novel treatment options are required to solve this problem. Botulinum toxin is an exotoxin generated by Clostridium botulinum. It disturbs the signal transmission at the neuromuscular and neuroglandular junction by inhibiting the acetylcholine release from the presynaptic nerve terminal. It has been widely used in neuromuscular, hypersecretory, and autonomic nerve system disorders. There have been a lot of published articles concerning the effect of this toxin on rhinitis symptoms. Based on the results of these reports, intranasal botulinum toxin A administration appears to be a safe and effective treatment method for decreasing rhinitis symptoms in rhinitis patients with a long-lasting effect. Botulinum toxin type A will be a good treatment option for the chronic rhinitis patients who are resistant to other treatment methods.

Comparison of oral toxicological properties of botulinum neurotoxin serotypes A and B.

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Cheng, Luisa W; Henderson, Thomas D

2011-07-01

Botulinum neurotoxins (BoNTs) are among the most potent biological toxins for humans. Of the seven known serotypes (A-G) of BoNT, serotypes A, B and E cause most of the foodborne intoxications in humans. BoNTs in nature are associated with non-toxic accessory proteins known as neurotoxin-associated proteins (NAPs), forming large complexes that have been shown to play important roles in oral toxicity. Using mouse intraperitoneal and oral models of botulism, we determined the dose response to both BoNT/B holotoxin and complex toxins, and compared the toxicities of BoNT/B and BoNT/A complexes. Although serotype A and B complexes have similar NAP composition, BoNT/B formed larger-sized complexes, and was approximately 90 times more lethal in mouse oral intoxications than BoNT/A complexes. When normalized by mean lethal dose, mice orally treated with high doses of BoNT/B complex showed a delayed time-to-death when compared with mice treated with BoNT/A complex. Furthermore, we determined the effect of various food matrices on oral toxicity of BoNT/A and BoNT/B complexes. BoNT/B complexes showed lower oral bioavailability in liquid egg matrices when compared to BoNT/A complexes. In summary, our studies revealed several factors that can either enhance or reduce the toxicity and oral bioavailability of BoNTs. Dissecting the complexities of the different BoNT serotypes and their roles in foodborne botulism will lead to a better understanding of toxin biology and aid future food risk assessments. Published by Elsevier Ltd.

Botulinum neurotoxin vaccines: Past history and recent developments.

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Rusnak, Janice M; Smith, Leonard A

2009-12-01

Botulinum toxin may cause a neuroparalytic illness that may result in respiratory failure and require prolonged mechanical ventilation. As medical resources needed for supportive care of botulism in a bioterrorist event may quickly overwhelm the local healthcare systems, biodefense research efforts have been directed towards the development of a vaccine to prevent botulism. While human botulism has been caused only by toxin serotypes A, B, and E (rarely serotype F), all seven known immunologically distinct toxin serotypes (A - G) may potentially cause intoxication in humans from a bioterrorist event. A pentavalent (ABCDE) botulinum toxoid (PBT) has been administered as an investigation new drug (IND) to at-risk individuals for nearly 50 years. Due to declining immunogenicity of the PBT, research efforts have been directed at development of both improved (less local reactogenicity) botulinum toxoids and recombinant vaccines as potential vaccine candidates to replace the PBT.

Botulinum toxin A for the Treatment of Overactive Bladder.

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Hsieh, Po-Fan; Chiu, Hung-Chieh; Chen, Kuan-Chieh; Chang, Chao-Hsiang; Chou, Eric Chieh-Lung

2016-02-29

The standard treatment for overactive bladder starts with patient education and behavior therapies, followed by antimuscarinic agents. For patients with urgency urinary incontinence refractory to antimuscarinic therapy, currently both American Urological Association (AUA) and European Association of Urology (EAU) guidelines suggested that intravesical injection of botulinum toxin A should be offered. The mechanism of botulinum toxin A includes inhibition of vesicular release of neurotransmitters and the axonal expression of capsaicin and purinergic receptors in the suburothelium, as well as attenuation of central sensitization. Multiple randomized, placebo-controlled trials demonstrated that botulinum toxin A to be an effective treatment for patients with refractory idiopathic or neurogenic detrusor overactivity. The urinary incontinence episodes, maximum cystometric capacity, and maximum detrusor pressure were improved greater by botulinum toxin A compared to placebo. The adverse effects of botulinum toxin A, such as urinary retention and urinary tract infection, were primarily localized to the lower urinary tract. Therefore, botulinum toxin A offers an effective treatment option for patients with refractory overactive bladder.

Botulinum Toxin and Muscle Atrophy: A Wanted or Unwanted Effect.

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Durand, Paul D; Couto, Rafael A; Isakov, Raymond; Yoo, Donald B; Azizzadeh, Babak; Guyuron, Bahman; Zins, James E

2016-04-01

While the facial rejuvenating effect of botulinum toxin type A is well known and widespread, its use in body and facial contouring is less common. We first describe its use for deliberate muscle volume reduction, and then document instances of unanticipated and undesirable muscle atrophy. Finally, we investigate the potential long-term adverse effects of botulinum toxin-induced muscle atrophy. Although the use of botulinum toxin type A in the cosmetic patient has been extensively studied, there are several questions yet to be addressed. Does prolonged botulinum toxin treatment increase its duration of action? What is the mechanism of muscle atrophy and what is the cause of its reversibility once treatment has stopped? We proceed to examine how prolonged chemodenervation with botulinum toxin can increase its duration of effect and potentially contribute to muscle atrophy. Instances of inadvertent botulinum toxin-induced atrophy are also described. These include the "hourglass deformity" secondary to botulinum toxin type A treatment for migraine headaches, and a patient with atrophy of multiple facial muscles from injections for hemifacial spasm. Numerous reports demonstrate that muscle atrophy after botulinum toxin type A treatment occurs and is both reversible and temporary, with current literature supporting the notion that repeated chemodenervation with botulinum toxin likely responsible for both therapeutic and incidental temporary muscle atrophy. Furthermore, duration of response may be increased with subsequent treatments, thus minimizing frequency of reinjection. Practitioners should be aware of the temporary and reversible effect of botulinum toxin-induced muscle atrophy and be prepared to reassure patients on this matter. © 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

Considerations on patient-related outcomes with the use of botulinum toxins: is switching products safe?

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Fraint A

2016-02-01

Full Text Available Avram Fraint,1 Padmaja Vittal,2 Cynthia Comella2 1Department of Neurological Sciences, 2Section of Movement Disorders, Rush University Medical Center, Chicago, IL, USA Introduction: Botulinum toxin (BoNT is the treatment of choice for many neurologic movement disorders, including blepharospasm, hemifacial spasm, and cervical dystonia. There are two serotypes approved for use by the US Food and Drug Administration: three brands of serotype A and one of serotype B. Many attempts have been made at establishing dose conversion ratios between brands and serotypes. This review focuses on the existing data comparing different formulations of the same BoNT serotypes as well as that comparing different serotypes with one another. We focus on existing data regarding switching from one formulation or serotype to another and will also discuss the issue of immunogenicity of BoNT. With this information as a foundation, recommendations on safety of switching agents are addressed. Method: Literature review searching PubMed and Google Scholar using the search terms “switching botox”, “dosing equivalency in botox”, and “comparing botox”. Results/conclusion: Overall, there are many studies that demonstrate the efficacy and safety of each of the brands of BoNTs used in clinical practice. However, determination of dosing equivalencies among these brands and serotypes is complex with inconsistencies among the studies. When switching from one brand to another, the clinician should be aware of these issues, and not make the assumption that such ratios exist. Tailoring the dosage of each brand of BoNT to the clinical situation is the most prudent treatment strategy rather than focusing closely on conversion factors and concerns for immunogenicity. Keywords: botulinum toxin, BoNT, abobotulinumtoxin A, onabotulinumtoxin A, incobotulinumtoxin A, rimabotulinumtoxin B

The botulinum toxin as a therapeutic agent: molecular and pharmacological insights

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Kukreja R

2015-12-01

Full Text Available Roshan Kukreja,1 Bal Ram Singh2 1Department of Chemistry and Biochemistry, University of Massachusetts, 2Botulinum Research Center, Institute of Advanced Sciences, Dartmouth, MA, USA Abstract: Botulinum neurotoxins (BoNTs, the most potent toxins known to mankind, are metalloproteases that act on nerve–muscle junctions to block exocytosis through a very specific and exclusive endopeptidase activity against soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE proteins of presynaptic vesicle fusion machinery. This very ability of the toxins to produce flaccid muscle paralysis through chemical denervation has been put to good use, and these potentially lethal toxins have been licensed to treat an ever expanding list of medical disorders and more popularly in the field of esthetic medicine. In most cases, therapeutic BoNT preparations are high-molecular-weight protein complexes consisting of BoNT, complexing proteins, and excipients. There is at least one isolated BoNT, which is free of complexing proteins in the market (Xeomin®. Each commercially available BoNT formulation is unique, differing mainly in molecular size and composition of complexing proteins, biological activity, and antigenicity. BoNT serotype A is marketed as Botox®, Dysport®, and Xeomin®, while BoNT type B is commercially available as Myobloc®. Nerve terminal intoxication by BoNTs is completely reversible, and the duration of therapeutic effects of BoNTs varies for different serotypes. Depending on the target tissue, BoNTs can block the cholinergic neuromuscular or cholinergic autonomic innervation of exocrine glands and smooth muscles. Therapeutic BoNTs exhibit a high safety and very limited adverse effects profile. Despite their established efficacy, the greatest concern with the use of therapeutic BoNTs is their propensity to elicit immunogenic reactions that might render the patient unresponsive to subsequent treatments, particularly in chronic

Botulinum Toxin in Neurogenic Detrusor Overactivity

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Carlos Arturo Levi D'Ancona

2012-09-01

Full Text Available Purpose To evaluate the effects of botulinum toxin on urodynamic parameters and quality of life in patients with neurogenic detrusor overactivity. Methods Thirty four adult patients with spinal cord injury and detrusor overactivity were selected. The patients received 300 units of botulinum toxin type A. The endpoints evaluated with the episodes of urinary incontinence and measured the maximum cystometric capacity, maximum amplitude of detrusor pressure and bladder compliance at the beginning and end of the study (24 weeks and evaluated the quality of life by applying the Qualiveen questionnaire. Results A significant decrease in the episodes of urinary incontinence was observed. All urodynamic parameters presented a significant improvement. The same was observed in the quality of life index and the specific impact of urinary problems scores from the Qualiveen questionnaire. Six patients did not complete the study, two due to incomplete follow-up, and four violated protocol and were excluded from the analyses. No systemic adverse events of botulinum toxin type A were reported. Conclusions A botulinum toxin type A showed a significantly improved response in urodynamics parameters and specific and general quality of life.

Botulinum toxin in the treatment of vocal fold nodules.

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Allen, Jacqui E; Belafsky, Peter C

2009-12-01

Promising new techniques in the management of vocal fold nodules have been developed in the past 2 years. Simultaneously, the therapeutic use of botulinum toxin has rapidly expanded. This review explores the use of botulinum toxin in treatment of vocal nodules and summarizes current therapeutic concepts. New microsurgical instruments and techniques, refinements in laser technology, radiosurgical excision and steroid intralesional injections are all promising new techniques in the management of vocal nodules. Botulinum toxin-induced 'voice rest' is a new technique we have employed in patients with recalcitrant nodules. Successful resolution of nodules is possible with this technique, without the risk of vocal fold scarring inherent in dissection/excision techniques. Botulinum toxin usage is exponentially increasing, and large-scale, long-term studies demonstrate its safety profile. Targeted vocal fold temporary paralysis induced by botulinum toxin injection is a new, well tolerated and efficacious treatment in patients with persistent vocal fold nodules.

The resurgence of botulinum toxin injection for strabismus in children.

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Mahan, Marielle; Engel, J Mark

2017-09-01

The present review discusses recent advances in the use of botulinum toxin for the management of strabismus in children. Botulinum toxin injection produces similar results compared to surgery for certain subtypes of strabismus, especially acute onset esotropia. It may be more effective in many subtypes of esotropia where surgery has been less reliable, including partially accommodative esotropia, esotropia associated with cerebral palsy, and thyroid eye disease. Small retrospective studies have demonstrated the efficacy of botulinum toxin in the treatment of many types of pediatric strabismus, providing some guidance for clinicians to determine which patients would benefit most from this intervention. Although administration of botulinum toxin is generally accepted as a reasonable option in select cases, many strabismus surgeons have not fully embraced the treatment, in part because of perceived disadvantages compared to surgery and difficulty in identifying subsets with the highest potential for therapeutic success. A recent study compared the administration of botulinum toxin in children with acute-onset esotropia to surgical correction and found botulinum toxin had a statistically equal success rate, but with the advantage of significantly less time under general anesthesia. In addition, botulinum toxin has been recently tried in patients with partially accommodative esotropia, esotropia associated with cerebral palsy, cyclic esotropia, and in patients with thyroid eye disease. The present review will discuss current clinical recommendations based on recent studies on the use of botulinum toxin in children with strabismus.

Botulinum toxin for treatment of glandular hypersecretory disorders.

LENUS (Irish Health Repository)

Laing, T A

2012-02-03

SUMMARY: The use of botulinum toxin to treat disorders of the salivary glands is increasing in popularity in recent years. Recent reports of the use of botulinum toxin in glandular hypersecretion suggest overall favourable results with minimal side-effects. However, few randomised clinical trials means that data are limited with respect to candidate suitability, treatment dosages, frequency and duration of treatment. We report a selection of such cases from our own department managed with botulinum toxin and review the current data on use of the toxin to treat salivary gland disorders such as Frey\\'s syndrome, excessive salivation (sialorrhoea), focal and general hyperhidrosis, excessive lacrimation and chronic rhinitis.

Treatment of Palatal Myoclonus with Botulinum Toxin Injection

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Mursalin M. Anis

2013-01-01

Full Text Available Palatal myoclonus is a rare cause of pulsatile tinnitus in patients presenting to the otolaryngology office. Rhythmic involuntary contractions of the palatal muscles produce the pulsatile tinnitus in these patients. Treatment of this benign but distressing condition with anxiolytics, anticonvulsants, and surgery has been largely unsuccessful. A few investigators have obtained promising results with botulinum toxin injection into the palatal muscles. We present a patient with palatal myoclonus who failed conservative treatment with anxiolytics. Unilateral injection of botulinum toxin into her tensor veli palatini muscle under electromyographic guidance resolved pulsatile tinnitus in her ipsilateral ear and unmasked pulsatile tinnitus in the contralateral ear. A novel method of following transient postinjection symptoms using a diary is presented in this study. Botulinum toxin dose must be titrated to achieve optimal results in each individual patient, analogous to titrations done for spasmodic dysphonia. Knowledge of the temporal onset of postinjection side effects and symptomatic relief may aid physicians in dose titration and surveillance. We present suggestions on titrating the botulinum toxin dose to optimal levels. A review of the literature on the use of botulinum toxin for palatal myoclonus and some common complications are discussed.

Cosmetic Effect of Botulinum Toxin In Focal Hyperhydrosis

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Jain S

2005-01-01

Full Text Available Hyperhydrosis of axillae, palm and sole is not a very uncommon problem. It leads to great embarrassment and considerable emotional stress to the individuals. Botulinum toxins prevent the release of acetylcholine at nerve terminals, therefore, reduces sweat secretion. Six patients of axillary and 4 patients of palmer and planter hyperhydrosis were treated with botulinum toxin. All patients experienced relatively satisfactory reduction of hyperhydrosis for period ranging between 4-7 months. No adverse effects were observed. Botulinum toxin therefore can be considered as an effective treatment in focal hyperhydrosis.

Botulinum toxin type A versus botulinum toxin type B for cervical dystonia.

Science.gov (United States)

Duarte, Gonçalo S; Castelão, Mafalda; Rodrigues, Filipe B; Marques, Raquel E; Ferreira, Joaquim; Sampaio, Cristina; Moore, Austen P; Costa, João

2016-10-26

This is an update of a Cochrane review first published in 2003. Cervical dystonia is the most common form of focal dystonia and is a disabling disorder characterised by painful involuntary head posturing. There are two available formulations of botulinum toxin, with botulinum toxin type A (BtA) usually considered the first line therapy for this condition. Botulinum toxin type B (BtB) is an alternative option, with no compelling theoretical reason why it might not be as- or even more effective - than BtA. To compare the efficacy, safety and tolerability of botulinum toxin type A (BtA) versus botulinum toxin type B (BtB) in people with cervical dystonia. To identify studies for this review we searched the Cochrane Movement Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, reference lists of articles and conference proceedings. All elements of the search, with no language restrictions, were last run in October 2016. Double-blind, parallel, randomised, placebo-controlled trials (RCTs) comparing BtA versus BtB in adults with cervical dystonia. Two independent authors assessed records, selected included studies, extracted data using a paper pro forma, and evaluated the risk of bias. We resolved disagreements by consensus or by consulting a third author. We performed meta-analyses using the random-effects model, for the comparison BtA versus BtB to estimate pooled effects and corresponding 95% confidence intervals (95% CI). No prespecified subgroup analyses were carried out. The primary efficacy outcome was improvement on any validated symptomatic rating scale, and the primary safety outcome was the proportion of participants with adverse events. We included three RCTs, all new to this update, of very low to low methodological quality, with a total of 270 participants.Two studies exclusively enrolled participants with a known positive response to BtA treatment. This raises concerns of population enrichment

Office-based endoscopic botulinum toxin injection in laryngeal movement disorders.

Science.gov (United States)

Kaderbay, A; Righini, C A; Castellanos, P F; Atallah, I

2018-06-01

Botulinum toxin injection is widely used for the treatment of laryngeal movement disorders. Electromyography-guided percutaneous injection is the technique most commonly used to perform intralaryngeal botulinum toxin injection. We describe an endoscopic approach for intralaryngeal botulinum toxin injection under local anaesthesia without using electromyography. A flexible video-endoscope with an operating channel is used. After local anaesthesia of the larynx by instillation of lidocaine, a flexible needle is inserted into the operating channel in order to inject the desired dose of botulinum toxin into the vocal and/or vestibular folds. Endoscopic botulinum toxin injection under local anaesthesia is a reliable technique for the treatment of laryngeal movement disorders. It can be performed by any laryngologist without the need for electromyography. It is easy to perform for the operator and comfortable for the patient. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Botulinum toxin treatment for facial palsy: A systematic review.

Science.gov (United States)

Cooper, Lilli; Lui, Michael; Nduka, Charles

2017-06-01

Facial palsy may be complicated by ipsilateral synkinesis or contralateral hyperkinesis. Botulinum toxin is increasingly used in the management of facial palsy; however, the optimum dose, treatment interval, adjunct therapy and performance as compared with alternative treatments have not been well established. This study aimed to systematically review the evidence for the use of botulinum toxin in facial palsy. The Cochrane central register of controlled trials (CENTRAL), MEDLINE(R) (1946 to September 2015) and Embase Classic + Embase (1947 to September 2015) were searched for randomised studies using botulinum toxin in facial palsy. Forty-seven studies were identified, and three included. Their physical and patient-reported outcomes are described, and observations and cautions are discussed. Facial asymmetry has a strong correlation to subjective domains such as impairment in social interaction and perception of self-image and appearance. Botulinum toxin injections represent a minimally invasive technique that is helpful in restoring facial symmetry at rest and during movement in chronic, and potentially acute, facial palsy. Botulinum toxin in combination with physical therapy may be particularly helpful. Currently, there is a paucity of data; areas for further research are suggested. A strong body of evidence may allow botulinum toxin treatment to be nationally standardised and recommended in the management of facial palsy. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Botulinum toxin for treatment of the focal dystonia.

Science.gov (United States)

Nakamura, Yusaku

2017-07-29

Dystonia is defined as a movement disorder characterized by sustained or intermittent muscles contraction causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are typically patterned and twisting, and may be tremulous. The precis diagnosis of dystonia is difficult for physicians because neurological brain imaging does not provide enough practical information. The diagnosis is depend on clinical experience of physicians. Botulinum toxin treatment is the accepted standard of care for patients with focal dystonia. Botulinum toxin treatment results in significant improvement of decreasing the symptom of dystonia. The success of treatment is dependent on muscle selection for treating involved muscles. Usually performance of botulinum toxin treatment is injected according to clinical experience of surface anatomy or clinical location method. However, the benefit of guidance of botulinum toxin treatment is improve outcome in dystonia. Injection techniques with ultra sound echogram or EMG guidance to identify dystonic muscles can be more benefit for patients.

Treatment of proctalgia fugax with botulinum A toxin.

Science.gov (United States)

Katsinelos, P; Kalomenopoulou, M; Christodoulou, K; Katsiba, D; Tsolkas, P; Pilpilidis, I; Papagiannis, A; Kapitsinis, I; Vasiliadis, I; Souparis, T

2001-11-01

Two recent studies described a temporal association between a high-amplitude and high-frequency myoelectrical activity of the anal sphincter and the occurrence of proctalgia, which suggest that paroxysmal hyperkinesis of the anus may cause proctalgia fugax. We describe a single case of proctalgia fugax responding to anal sphincter injection of Clostridium botulinum type A toxin. The presumed aetiology of proctalgia fugax is discussed and the possible mechanism of action of botulinum toxin (BTX) in this condition is outlined. Botulinum A toxin seems to be a promising treatment for patients with proctalgia fugax, and further trials appear to be worthwhile for this condition, which has been described as incurable.

Treatment of Gastrointestinal Sphincters Spasms with Botulinum Toxin A

Directory of Open Access Journals (Sweden)

Giuseppe Brisinda

2015-05-01

Full Text Available Botulinum toxin A inhibits neuromuscular transmission. It has become a drug with many indications. The range of clinical applications has grown to encompass several neurological and non-neurological conditions. One of the most recent achievements in the field is the observation that botulinum toxin A provides benefit in diseases of the gastrointestinal tract. Although toxin blocks cholinergic nerve endings in the autonomic nervous system, it has also been shown that it does not block non-adrenergic non-cholinergic responses mediated by nitric oxide. This has promoted further interest in using botulinum toxin A as a treatment for overactive smooth muscles and sphincters. The introduction of this therapy has made the treatment of several clinical conditions easier, in the outpatient setting, at a lower cost and without permanent complications. This review presents current data on the use of botulinum toxin A in the treatment of pathological conditions of the gastrointestinal tract.

Update on botulinum toxin and dermal fillers.

Science.gov (United States)

Berbos, Zachary J; Lipham, William J

2010-09-01

The art and science of facial rejuvenation is an ever-evolving field of medicine, as evidenced by the continual development of new surgical and nonsurgical treatment modalities. Over the past 10 years, the use of botulinum toxin and dermal fillers for aesthetic purposes has risen sharply. Herein, we discuss properties of several commonly used injectable products and provide basic instruction for their use toward the goal of achieving facial rejuvenation. The demand for nonsurgical injection-based facial rejuvenation products has risen enormously in recent years. Used independently or concurrently, botulinum toxin and dermal filler agents offer an affordable, minimally invasive approach to facial rejuvenation. Botulinum toxin and dermal fillers can be used to diminish facial rhytides, restore facial volume, and sculpt facial contours, thereby achieving an aesthetically pleasing, youthful facial appearance.

Affinity chromatography of tetanus toxin, tetanus toxoid, and botulinum A toxin on synaptosomes, and differentiation of their acceptors

Energy Technology Data Exchange (ETDEWEB)

Habermann, E [Giessen Univ. (Germany, F.R.). Pharmakologisches Inst.

1976-01-01

/sup 125/I-labelled tetanus toxin and /sup 125/I-labelled botulinum A neurotoxin are known to be specifically bound to brain synaptosomes. In order to discriminate between active toxin and inactive admixtures present in the starting material or arising during iodination, synaptosome columns were prepared using bromacetylcellulose and/or kieselgur (Celite) as carriers. Both types of columns adsorb the toxins from low ionic strength medium and release them if the pH and ionic strength are raised. Botulinum toxin was eluted with lower ionic strength than tetanus toxin, and could be freed from nontoxic admixtures. Analysis by affinity chromatography disclosed partially toxoided tetanus toxin in both labelled and unlabelled toxin samples. High concentrations of formaldehyde (0.5%) destroyed both toxicity and affinity to the synaptosomes of tetanus toxin. Low concentrations of formaldehyde (0.05%) yielded a derivative of low toxicity which was still, however less firmly, bound to synaptosomes. Tetanus and botulinum toxin differ by their acceptors. Whereas unlabelled botulinum toxin is unable to compete with labelled tetanus toxin, unlabelled tetanus toxin slightly competes with botulinum toxin. Both labelled toxins display anomalous binding behaviour in that they cannot be displaced completely even with a large excess of unlabelled toxin.

Affinity chromatography of tetanus toxin, tetanus toxoid, and botulinum A toxin on synaptosomes, and differentiation of their acceptors

International Nuclear Information System (INIS)

Habermann, E.

1976-01-01

125 I-labelled tetanus toxin and 125 I-labelled botulinum A neurotoxin are known to be specifically bound to brain synaptosomes. In order to discriminate between active toxin and inactive admixtures present in the starting material or arising during iodination, synaptosome columns were prepared using bromacetylcellulose and/or kieselgur (Celite) as carriers. Both types of columns adsorb the toxins from low ionic strength medium and release them if the pH and ionic strength are raised. Botulinum toxin was eluted with lower ionic strength than tetanus toxin, and could be freed from nontoxic admixtures. Analysis by affinity chromatography disclosed partially toxoided tetanus toxin in both labelled and unlabelled toxin samples. High concentrations of formaldehyde (0.5%) destroyed both toxicity and affinity to the synaptosomes of tetanus toxin. Low concentrations of formaldehyde (0.05%) yielded a derivative of low toxicity which was still, however less firmly, bound to synaptosomes. Tetanus and botulinum toxin differ by their acceptors. Whereas unlabelled botulinum toxin is unable to compete with labelled tetanus toxin, unlabelled tetanus toxin slightly competes with botulinum toxin. Both labelled toxins display anomalous binding behaviour in that they cannot be displaced completely even with a large excess of unlabelled toxin. (orig.) [de

Efficacy of botulinum toxins on bruxism: an evidence-based review.

Science.gov (United States)

Long, Hu; Liao, Zhengyu; Wang, Yan; Liao, Lina; Lai, Wenli

2012-02-01

The objective of this study was to assess the efficacy of botulinum toxins on bruxism. Electronic databases (PubMed, Embase and Science Citation Index), websites (Cochrane Central Register of Controlled Trials and ClinicalTrials.gov) and the literature database of SIGLE (System for Information on Grey Literature in Europe) were searched from January 1990 to April 2011 for randomised controlled trials or nonrandomised studies assessing the efficacy of botulinum toxins on bruxism. There was no language restriction. Through a predefined search strategy, we retrieved 28 studies from PubMed, 94 from Embase, 60 from the Science Citation Index, two ongoing clinical trials and two from the Cochrane Central Register of Controlled Trials. Of these, only four studies met our inclusion criteria and were finally included. Of the four included studies, two were randomised controlled trials and two were controlled before-and-after studies. These studies showed that botulinum toxin injections can reduce the frequency of bruxism events, decrease bruxism-induced pain levels and satisfy patients' self-assessment with regard to the effectiveness of botulinum toxins on bruxism. In comparison with oral splint, botulinum toxins are equally effective on bruxism. Furthermore, botulinum toxin injections at a dosage of bruxism and are safe to use. Therefore, they can be used clinically for otherwise healthy patients with bruxism. © 2012 FDI World Dental Federation.

Botulinum toxin therapy for limb dystonias.

Science.gov (United States)

Yoshimura, D M; Aminoff, M J; Olney, R K

1992-03-01

We investigated the effectiveness of botulinum toxin in 17 patients with limb dystonias (10 with occupational cramps, three with idiopathic dystonia unrelated to activity, and two each with post-stroke and parkinsonian dystonia) in a placebo-controlled, blinded study. We identified affected muscles clinically and by recording the EMG from implanted wire electrodes at rest and during performance of tasks that precipitated abnormal postures. There were three injections given with graded doses of toxin (average doses, 5 to 10, 10 to 20, and 20 to 40 units per muscle) and one with placebo, in random order. Subjective improvement occurred after 53% of injections of botulinum toxin, and this was substantial in 24%. Only one patient (7%) improved after placebo injection. Subjective improvement occurred in 82% of patients with at least one dose of toxin, lasting for 1 to 4 months. Response rates were similar between clinical groups. Objective evaluation failed to demonstrate significant improvement following treatment with toxin compared with placebo. The major side effect was transient focal weakness after 53% of injections of toxin.

Bupivacaine and botulinum toxin to treat comitant strabismus

Directory of Open Access Journals (Sweden)

Luisa Moreira Hopker

2012-04-01

Full Text Available PURPOSE: To evaluate the change in ocular motility and muscle thickness measured with ultrasonography after intramuscular injection of bupivacaine and botulinum toxin A. METHODS: Eight patients (five female were enrolled to measure ocular motility prior and 1, 7, 30 and 180 days after one injection of 2 ml of 1.5% bupivacaine and 2.5 U of botulinum toxin A in agonist and antagonist muscles, respectively, of eight amblyopic eyes. Muscle thickness was measured prior and on days 1, 7 and 30 after injection using 10-MHz ultrasonography (eyelid technique. RESULTS: Mean change in alignment was 10 prism diopters after 180 days (n=6. An average increase of 1.01 mm in muscle thickness was observed after 30 days of bupivacaine injection and 0.28 mm increase was observed after botulinum toxin A injection, as measured by ultrasonography. Lateral rectus muscles injected with bupivacaine had a mean increase of 1.5 mm in muscle thickness. CONCLUSION: In this study, a change in ocular motility was observed after 180 days of intramuscular injection of bupivacaine and botulinum toxin in horizontal extraocular muscles. Overall, there was an increase of muscle thickness in both botulinum toxinum A and bupivacaine injected muscles after 30 days of injection when measured by ultrasonography. This change was more pronounced on lateral rectus muscles after bupivacaine injection.

A Medical Research and Evaluation Facility (MREF) and Studies Supporting the Medical Chemical Defense Program. Evaluation of the Passive Protection Against Five Serotypes of Botulinum Toxin Provided by Botulinum Human Immune Globulin in an Animal Model

National Research Council Canada - National Science Library

Olson, Carl

1998-01-01

Pentavalent (ABCDE) botulinum toxoid vaccine is intended for use as a prophylactic measure to protect combat troops against the lethal effects of botulinum toxins A-E, a group of toxins considered to be a serious biological warfare threat...

Topical Botulinum Toxin

OpenAIRE

Collins, Ashley; Nasir, Adnan

2010-01-01

Nanotechnology is a rapidly growing discipline that capitalizes on the unique properties of matter engineered on the nanoscale. Vehicles incorporating nanotechnology have led to great strides in drug delivery, allowing for increased active ingredient stability, bioavailability, and site-specific targeting. Botulinum toxin has historically been used for the correction of neurological and neuromuscular disorders, such as torticollis, blepharospasm, and strabismus. Recent dermatological indicati...

Prevalence of toxin-producing Clostridium botulinum associated with the macroalga Cladophora in three Great Lakes: growth and management

Science.gov (United States)

Chun, Chan Lan; Kahn, Chase I.; Borchert, Andrew J.; Byappanahalli, Muruleedhara N.; Whitman, Richard L.; Peller, Julie R.; Pier, Christina; Lin, Guangyun; Johnson, Eric A.; Sadowsky, Michael J.

2015-01-01

The reemergence of avian botulism caused by Clostridium botulinum type E has been observed across the Great Lakes in recent years. Evidence suggests an association between the nuisance algae, Cladophoraspp., and C. botulinum in nearshore areas of the Great Lakes. However, the nature of the association between Cladophora and C. botulinum is not fully understood due, in part, to the complex food web interactions in this disease etiology. In this study, we extensively evaluated their association by quantitatively examining population size and serotypes of C. botulinum in algal mats collected from wide geographic areas in lakes Michigan, Ontario, and Erie in 2011–2012 and comparing them with frequencies in other matrices such as sand and water. A high prevalence (96%) of C. botulinum type E was observed inCladophora mats collected from shorelines of the Great Lakes in 2012. Among the algae samples containing detectable C. botulinum, the population size of C. Botulinum type E was 100–104 MPN/g dried algae, which was much greater (up to 103 fold) than that found in sand or the water column, indicating thatCladophora mats are sources of this pathogen. Mouse toxinantitoxin bioassays confirmed that the putativeC. botulinum belonged to the type E serotype. Steam treatment was effective in reducing or eliminating C. botulinum type E viable cells in Cladophora mats, thereby breaking the potential transmission route of toxin up to the food chain. Consequently, our data suggest that steam treatment incorporated with a beach cleaning machine may be an effective treatment of Cladophora-borne C. botulinum and may reduce bird mortality and human health risks.

Usefulness of intra-articular botulinum toxin injections. A systematic review.

Science.gov (United States)

Khenioui, Hichem; Houvenagel, Eric; Catanzariti, Jean François; Guyot, Marc Alexandre; Agnani, Olivier; Donze, Cécile

2016-03-01

Botulinum toxin is a proven and widely used treatment for numerous conditions characterized by excessive muscular contractions. Recent studies have assessed the analgesic effect of botulinum toxin in joint pain and started to unravel its mechanisms. We searched the international literature via the Medline database using the term "intraarticular botulinum toxin injection" combined with any of the following terms: "knee", "ankle", "shoulder", "osteoarthritis", "adhesive capsulitis of the shoulder". Of 16 selected articles about intraarticular botulinum toxin injections, 7 were randomized controlled trials done in patients with osteoarthritis, adhesive capsulitis of the shoulder, or chronic pain after joint replacement surgery. Proof of anti-nociceptive effects was obtained in some of these indications and the safety and tolerance profile was satisfactory. The studies are heterogeneous. The comparator was usually a glucocorticoid or a placebo; a single study used hyaluronic acid. Pain intensity was the primary outcome measure. The number of randomized trials and sample sizes are too small to provide a satisfactory level of scientific evidence or statistical power. Unanswered issues include the effective dosage and the optimal dilution and injection modalities of botulinum toxin. Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Therapeutic Approaches of Botulinum Toxin in Gynecology

OpenAIRE

Marius Alexandru Moga; Oana Gabriela Dimienescu; Andreea Bălan; Ioan Scârneciu; Barna Barabaș; Liana Pleș

2018-01-01

Botulinum toxins (BoNTs) are produced by several anaerobic species of the genus Clostridium and, although they were originally considered lethal toxins, today they find their usefulness in the treatment of a wide range of pathologies in various medical specialties. Botulinum neurotoxin has been identified in seven different isoforms (BoNT-A, BoNT-B, BoNT-C, BoNT-D, BoNT-E, BoNT-F, and BoNT-G). Neurotoxigenic Clostridia can produce more than 40 different BoNT subtypes and, recently, a new BoNT...

Botulinum toxin in medicine and cosmetology – two hundred years’ history and new perspectives

Directory of Open Access Journals (Sweden)

Małgorzata Zbrojkiewicz

2018-04-01

of coding genes and by the duration of the therapeutic effect. American physician Allan B. Scott was the first to demonstrate the use of botulinum toxin for medical purposes. Nowadays, botulinum toxin type A is widely used in medicine. Botulinum toxin injections are not only one of the most popular non-surgical aesthetic-cosmetic procedures, but are also widely used in neurology, ophthalmology and dermatology. The therapeutic potential of botulinum toxin has not been exhausted yet. Currently, many clinical trials are underway to extend the therapeutic indications of botulinum toxin and to improve its safety. Due to the huge development in medicine, botulinum toxin is today not only associated with aesthetic procedures and improvement in appearance, but also with raising the quality of life for people suffering from diseases with excessive muscle contraction and with other neuromuscular disorders.

Protective vaccination with a recombinant fragment of Clostridium botulinum neurotoxin serotype A expressed from a synthetic gene in Escherichia coli.

OpenAIRE

Clayton, M A; Clayton, J M; Brown, D R; Middlebrook, J L

1995-01-01

A completely synthetic gene encoding fragment C, a approximately 50-kDa fragment, of botulinum neurotoxin serotype A was constructed from oligonucleotides. The gene was expressed in Escherichia coli, and full-sized product was produced as judged by Western blot (immunoblot) analysis. Crude extracts of E. coli expressing the gene were used to vaccinate mice and evaluate their survival against challenge with active toxin. Mice given three subcutaneous vaccinations were protected against an intr...

Comparison of oral toxicological properties of botulinum neurotoxin

Science.gov (United States)

Botulinum neurotoxins (BoNTs) are among the most potent biological toxins for humans. Of the seven known serotypes (A-G) of BoNT, serotypes A, B and E cause most of the foodborne intoxications in humans. BoNTs in nature are associated with non-toxic accessory proteins known as neurotoxin-associated ...

Probiotic Microorganisms Inhibit Epithelial Cell Internalization of Botulinum Neurotoxin Serotype A

Science.gov (United States)

Lam, Tina I.; Tam, Christina C.; Stanker, Larry H.; Cheng, Luisa W.

2016-01-01

Botulinum neurotoxins (BoNTs) are some of the most poisonous natural toxins known to man and are threats to public health and safety. Previous work from our laboratory showed that both BoNT serotype A complex and holotoxin can bind and transit through the intestinal epithelia to disseminate in the blood. The timing of BoNT/A toxin internalization was shown to be comparable in both the Caco-2 in vitro cell culture and in the oral mouse intoxication models. Probiotic microorganisms have been extensively studied for their beneficial effects in not only maintaining the normal gut mucosa but also protection from allergens, pathogens, and toxins. In this study, we evaluate whether probiotic microorganisms will block BoNT/A uptake in the in vitro cell culture system using Caco-2 cells. Several probiotics tested (Saccharomyces boulardii, Lactobacillus acidophilus, Lactobacillus rhamnosus LGG, and Lactobacillus reuteri) blocked BoNT/A uptake in a dose-dependent manner whereas a non-probiotic strain of Escherichia coli did not. We also showed that inhibition of BoNT/A uptake was not due to the degradation of BoNT/A nor by sequestration of toxin via binding to probiotics. These results show for the first time that probiotic treatment can inhibit BoNT/A binding and internalization in vitro and may lead to the development of new therapies. PMID:27999281

Probiotic Microorganisms Inhibit Epithelial Cell Internalization of Botulinum Neurotoxin Serotype A

Directory of Open Access Journals (Sweden)

Tina I. Lam

2016-12-01

Full Text Available Botulinum neurotoxins (BoNTs are some of the most poisonous natural toxins known to man and are threats to public health and safety. Previous work from our laboratory showed that both BoNT serotype A complex and holotoxin can bind and transit through the intestinal epithelia to disseminate in the blood. The timing of BoNT/A toxin internalization was shown to be comparable in both the Caco-2 in vitro cell culture and in the oral mouse intoxication models. Probiotic microorganisms have been extensively studied for their beneficial effects in not only maintaining the normal gut mucosa but also protection from allergens, pathogens, and toxins. In this study, we evaluate whether probiotic microorganisms will block BoNT/A uptake in the in vitro cell culture system using Caco-2 cells. Several probiotics tested (Saccharomyces boulardii, Lactobacillus acidophilus, Lactobacillus rhamnosus LGG, and Lactobacillus reuteri blocked BoNT/A uptake in a dose-dependent manner whereas a non-probiotic strain of Escherichia coli did not. We also showed that inhibition of BoNT/A uptake was not due to the degradation of BoNT/A nor by sequestration of toxin via binding to probiotics. These results show for the first time that probiotic treatment can inhibit BoNT/A binding and internalization in vitro and may lead to the development of new therapies.

Headache and botulinum toxin

OpenAIRE

Porta, M.; Camerlingo, M.

2005-01-01

The authors discuss clinical and international experience about botulinum toxins (BTX types A and B) in headache treatment. Data from literature suggest good results for the treatment of tensiontype headache, migraine and chronic tension–type headache. In the present paper mechanisms of action and injection sites will also be discussed.

[Bruxism, temporo-mandibular dysfunction and botulinum toxin].

Science.gov (United States)

Chikhani, L; Dichamp, J

2003-07-01

Tooth grinding and tooth clenching are unvoluntary mainly nocturnal habits that result in an hypertrophy of masseter and temporalis muscles with an unbalance between opening and closing muscles of the jaw and lead to an alteration of mandibular condyles movements and to hyper pressure in the temporo-mandibular joints (TMJ) which can generate severe pain. Intra muscular injections of botulinum toxin permit to restablish the balance between closing and opening muscles, to relieve pain, to treat masseteric hypertrophy with improvement of face outline and to recover a normal cinetic of temporo-mandibular joints. Moreover, botulinum toxin injections permit to quit habits of tooth grinding and clenching and one single session of injections is curative for 2/3 of the patients. There are no side effects apart from slight diffusion to superficial muscles of the face resulting in a "fixed" smile for about 6 to 8 weeks. So injections of botulinum toxin in masseter and temporalis muscles are an efficient treatment of bruxism and TMJ dysfunction, cheap with no lasting side effect.

Failure of botulinum toxin injection for neurogenic detrusor overactivity: Switch of toxin versus second injection of the same toxin.

Science.gov (United States)

Peyronnet, Benoit; Castel-Lacanal, Evelyne; Manunta, Andréa; Roumiguié, Mathieu; Marque, Philippe; Rischmann, Pascal; Gamé, Xavier

2015-12-01

To evaluate the efficacy of a second injection of the same toxin versus switching to a different botulinum toxin A after failure of a first detrusor injection in patients with neurogenic detrusor overactivity. The charts of all patients who underwent detrusor injections of botulinum toxin A (either abobotulinumtoxinA or onabotulinumtoxinA) for the management of neurogenic detrusor overactivity at a single institution were retrospectively reviewed. Patients in whom a first detrusor injection had failed were included in the present study. They were managed by a second injection of the same toxin at the same dosage or by a new detrusor injection using a different botulinum toxin A. Success was defined as a resolution of urgency, urinary incontinence and detrusor overactivity in a patient self-catheterizing seven times or less per 24 h. A total of 58 patients were included for analysis. A toxin switch was carried out in 29 patients, whereas the other 29 patients received a reinjection of the same toxin at the same dose. The success rate was higher in patients who received a toxin switch (51.7% vs. 24.1%, P = 0.03). Patients treated with a switch from abobotulinumtoxinA to onabotulinumtoxinA and those treated with a switch from onabotulinumtoxinA to abobotulinumtoxinA had similar success rates (52.9% vs. 50%, P = 0.88). After failure of a first detrusor injection of botulinum toxin for neurogenic detrusor overactivity, a switch to a different toxin seems to be more effective than a second injection of the same toxin. The replacement of onabotulinumtoxin by abobotulinumtoxin or the reverse provides similar results. © 2015 The Japanese Urological Association.

Botulinum toxin for motor and phonic tics in Tourette's syndrome.

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Pandey, Sanjay; Srivanitchapoom, Prachaya; Kirubakaran, Richard; Berman, Brian D

2018-01-05

Gilles de la Tourette syndrome, or Tourette's syndrome, is defined as the presence of both motor and vocal (phonic) tics for more than 12 months, that manifest before the age of 18 years, in the absence of secondary causes. Treatment of motor and phonic tics is difficult and challenging. To determine the safety and effectiveness of botulinum toxin in treating motor and phonic tics in people with Tourette's syndrome, and to analyse the effect of botulinum toxin on premonitory urge and sensory tics. We searched the Cochrane Movement Disorders Group Trials Register, CENTRAL, MEDLINE, and two trials registers to 25 October 2017. We reviewed reference lists of relevant articles for additional trials. We considered all randomised, controlled, double-blind studies comparing botulinum toxin to placebo or other medications for the treatment of motor and phonic tics in Tourette's syndrome for this review. We sought both parallel group and cross-over studies of children or adults, at any dose, and for any duration. We followed standard Cochrane methods to select studies, assess risk of bias, extract and analyse data. All authors independently abstracted data onto standardized forms; disagreements were resolved by mutual discussion. Only one randomised placebo-controlled, double-blind cross-over study met our selection criteria. In this study, 20 participants with motor tics were enrolled over a three-year recruitment period; 18 (14 of whom had a diagnosis of Tourette's syndrome) completed the study; in total, 21 focal motor tics were treated. Although we considered most bias domains to be at low risk of bias, the study recruited a small number of participants with relatively mild tics and provided limited data for our key outcomes. The effects of botulinum toxin injections on tic frequency, measured by videotape or rated subjectively, and on premonitory urge, are uncertain (very low-quality evidence). The quality of evidence for adverse events following botulinum toxin was

Characterization of Hemagglutinin Negative Botulinum Progenitor Toxins

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Suzanne R. Kalb

2017-06-01

Full Text Available Botulism is a disease involving intoxication with botulinum neurotoxins (BoNTs, toxic proteins produced by Clostridium botulinum and other clostridia. The 150 kDa neurotoxin is produced in conjunction with other proteins to form the botulinum progenitor toxin complex (PTC, alternating in size from 300 kDa to 500 kDa. These progenitor complexes can be classified into hemagglutinin positive or hemagglutinin negative, depending on the ability of some of the neurotoxin-associated proteins (NAPs to cause hemagglutination. The hemagglutinin positive progenitor toxin complex consists of BoNT, nontoxic non-hemagglutinin (NTNH, and three hemagglutinin proteins; HA-70, HA-33, and HA-17. Hemagglutinin negative progenitor toxin complexes contain BoNT and NTNH as the minimally functional PTC (M-PTC, but not the three hemagglutinin proteins. Interestingly, the genome of hemagglutinin negative progenitor toxin complexes comprises open reading frames (orfs which encode for three proteins, but the existence of these proteins has not yet been extensively demonstrated. In this work, we demonstrate that these three proteins exist and form part of the PTC for hemagglutinin negative complexes. Several hemagglutinin negative strains producing BoNT/A, /E, and /F were found to contain the three open reading frame proteins. Additionally, several BoNT/A-containing bivalent strains were examined, and NAPs from both genes, including the open reading frame proteins, were associated with BoNT/A. The open reading frame encoded proteins are more easily removed from the botulinum complex than the hemagglutinin proteins, but are present in several BoNT/A and /F toxin preparations. These are not easily removed from the BoNT/E complex, however, and are present even in commercially-available purified BoNT/E complex.

Clostridium botulinum neurotoxin type B is heat-stable in milk and not inactivated by pasteurization.

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Rasooly, Reuven; Do, Paula M

2010-12-08

Foodborne botulism is caused by the ingestion of foods containing botulinum neurotoxins (BoNTs). To study the heat stability of Clostridium botulinum neurotoxins, we needed to measure and compare the activity of botulinum neurotoxins, serotypes A and B, under various pasteurization conditions. Currently, the only accepted assay to detect active C. botulinum neurotoxin is an in vivo mouse bioassay, which raises ethical concerns with regard to the use of experimental animals. In this study, noninvasive methods were used to simultaneously detect and distinguish between active BoNT serotypes A and B in one reaction and sample. We developed an enzymatic activity assay employing internally quenched fluorogenic peptides corresponding to SNAP-25, for BoNT-A, and VAMP2, for BoNT-B, as an alternative method to the mouse bioassay. Because each peptide is labeled with different fluorophores, we were able to distinguish between these two toxins. We used this method to analyze the heat stability of BoNT-A and BoNT-B. This study reports that conventional milk pasteurization (63 °C, 30 min) inactivated BoNT serotype A; however, serotype B is heat-stable in milk and not inactivated by pasteurization. Using this activity assay, we also showed that the commonly used food processes such as acidity and pasteurization, which are known to inhibit C. botulinum growth and toxin production, are more effective in inactivating BoNT serotype A than serotype B when conventional pasteurization (63 °C, 30 min) is used.

[Botulinum toxin type A in headache treatment : Established and experimental indications].

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Gaul, C; Holle-Lee, D; Straube, A

2016-08-01

In recent years botulinum toxin type A has been used increasingly more in the treatment of specific headache disorders. Especially regarding chronic migraine with and without combined medication overuse, convincing randomized studies have proven the efficacy of this treatment option and have led to approval for this indication. Regarding other headache entities, such as episodic migraine, tension-type headache, trigeminal autonomic cephalalgia (TAC), neuralgic, neuropathic and myofascial pain, currently available scientific data on the efficacy of botulinum toxin type A are scarce and often ambiguous. The exact underlying mechanisms of the influence of botulinum toxin type A on the pathophysiology of headache are not completely clear but an influence on the release of calcitonin gene-related peptide (CGRP) seems to play a crucial role. This article summarizes the most important studies as well as experiences of treatment with botulinum toxin type A regarding different headache entities.

Use of intradermal botulinum toxin to reduce sebum production and facial pore size.

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Shah, Anil R

2008-09-01

Review the safety profile and subjective efficacy of intradermal botulinum toxin type A in facial pore size and sebum production. Retrospective analysis of 20 patients. Twenty consecutive patients with a single application of intradermal botulinum toxin type A were examined: Patients (17/20) noted an improvement in sebum production and a decrease in pores size at 1 month after injection. No complications were observed, and 17/20 patients were satisfied with the procedure. Preliminary data suggests that intradermal botulinum toxin may play a role in decreasing sebum production. Further quantitive study may be necessary to determine effects of intradermal botulinum toxin on pore size.

Botulinum toxin: The Midas touch.

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Shilpa, P S; Kaul, Rachna; Sultana, Nishat; Bhat, Suraksha

2014-01-01

Botulinum Toxin (BT) is a natural molecule produced during growth and autolysis of bacterium called Clostridium botulinum. Use of BT for cosmetic purposes has gained popularity over past two decades, and recently, other therapeutic uses of BT has been extensively studied. BT is considered as a minimally invasive agent that can be used in the treatment of various orofacial disorders and improving the quality of life in such patients. The objective of this article is to review the nature, mechanism of action of BT, and its application in various head and neck diseases.

Botulinum toxin in bruxism treatment

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Piotr Piech

2017-07-01

Full Text Available Introduction: Bruxism is defined as abnormal, fixed, unconscious chewing organ function, deviating qualitatively and quantitatively from normal function. Another definition speaks of motor dysfunction in the mouth, characterized by grinding and clenching of the teeth, occurring during sleep. The etiology of this disorder has not been explained until now, but it is believed to be related to localized, mental, nervous and neurotransmitter disorders. Purpose: The aim of the study is to review literature and knowledge about the use of botulinum toxin in the treatment of bruxism. Methods of treatment: The patient reports to the physician usually after a distressing, difficult to locate pain. The basis for proper treatment is to detect parafunctions and to make the patient aware of their existence. Diagnostic symptoms include dentinal lesions, recesses, enamel cracks and abfractive cavities, as well as changes in the mucosal area of the cheeks. Treatment begins with the use of an occlusive therapy to relax muscles, reduce parafunction and relieve pain. In the form of severe pain, NSAIDs are introduced and, if necessary, anxiolytics, sedatives and antidepressants. In the absence of response to the treatment used, botulinum toxin type A injections are used. The dose of the agent depends on the initial muscle tone and the effect of decrease in its activity is maintained for 4 to 6 months. Conclusions: The use of botulinum toxin makes it possible to selectively exclude overactive muscles, which is a great advantage over other techniques. An additional benefit of this therapy is achieved good cosmetic effect, reversible effect and minimal amount of side effects.

Ultrasound-guided botulinum toxin injections

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S. E. Khatkova

2016-01-01

Full Text Available One of the key conditions for achieving the desirable result during botulinum toxin therapy for muscular dystonia, spasticity, and other diseases accompanied by spasm, pain, and autonomic dysfunction (dystonias, spasticity, etc. is the proper administration of the agent into the muscles directly involved in the pathological process. The exact entry of botulinum toxin into the target muscles is essential for successful and safe treatment because its injection into a normal muscle may cause side effects. The most common errors are the incorrect depth and incorrect direction of a needle on insertion. Therefore, the exact injection of the agent particularly into the shallow and deep muscles is a difficult task even for an experienced specialist and requires the use of controlling methods.The European Consensus on Botulinum Toxin Therapy points out that various injection techniques are needed for the better identification of necessary muscles. However, there are currently no reports on the clear advantage of any technique. In our country, injections using palpation and anatomical landmarks have been widely used in routine practice so far; electromyographic monitoring and electrostimulation have been less frequently applied. In recent years, the new method ultrasound-guided injection has continued to grow more popular. This effective, accessible, and easy-to-use method makes it possible to manage a real-time injection process and to ensure the exact entry of the agent into the muscle. This paper is dedicated to a comparative analysis of different injection methods and to a description of the ultrasound-guided technique and its advantages over others. 

Outcomes of Buccinator Treatment With Botulinum Toxin in Facial Synkinesis.

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Patel, Priyesh N; Owen, Scott R; Norton, Cathey P; Emerson, Brandon T; Bronaugh, Andrea B; Ries, William R; Stephan, Scott J

2018-05-01

The buccinator, despite being a prominent midface muscle, has been previously overlooked as a target in the treatment of facial synkinesis with botulinum toxin. To evaluate outcomes of patients treated with botulinum toxin to the buccinator muscle in the setting of facial synkinesis. Prospective cohort study of patients who underwent treatment for facial synkinesis with botulinum toxin over multiple treatment cycles during a 1-year period was carried out in a tertiary referral center. Botulinum toxin treatment of facial musculature, including treatment cycles with and without buccinator injections. Subjective outcomes were evaluated using the Synkinesis Assessment Questionnaire (SAQ) prior to injection of botulinum toxin and 2 weeks after treatment. Outcomes of SAQ preinjection and postinjection scores were compared in patients who had at least 1 treatment cycle with and without buccinator injections. Subanalysis was performed on SAQ questions specific to buccinator function (facial tightness and lip movement). Of 84 patients who received botulinum toxin injections for facial synkinesis, 33 received injections into the buccinator muscle. Of the 33, 23 met inclusion criteria (19 [82.6%] women; mean [SD] age, 46 [10] years). These patients presented for 82 treatment visits, of which 44 (53.6%) involved buccinator injections and 38 (46.4%) were without buccinator injections. The most common etiology of facial paralysis included vestibular schwannoma (10 [43.5%] participants) and Bell Palsy (9 [39.1%] participants). All patients had improved posttreatment SAQ scores compared with prebotulinum scores regardless of buccinator treatment. Compared with treatment cycles in which the buccinator was not addressed, buccinator injections resulted in lower total postinjection SAQ scores (45.9; 95% CI, 38.8-46.8; vs 42.8; 95% CI, 41.3-50.4; P = .43) and greater differences in prebotox and postbotox injection outcomes (18; 95% CI, 16.2-21.8; vs 19; 95% CI, 14.2-21.8; P�

Comparing two botulinum toxin type A formulations using manufacturers' product summaries.

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Wenzel, R; Jones, D; Borrego, J A

2007-08-01

Because of the unique pharmacology and clinical versatility of botulinum toxin (BoNT), particularly BoNT serotype A (BoNTA), a need exists for discussion of the current data on similarities and differences between two BoNTA products, BOTOX and Dysport. We compared the physiochemical and pharmacological properties of BOTOX and Dysport using information from the Summary of Product Characteristics (SmPC) documents from a number of countries around the world. Our analysis based on the SmPC documents demonstrated distinct differences in physical characteristics, breadth of approved indications, dosing and administration, and the incidence and severity of adverse events. BOTOX and Dysport are not bioequivalent. Many of the differences between BOTOX and Dysport discussed within are probably related to the differences in their physical characteristics.

Treatment of anismus in intractable constipation with botulinum A toxin.

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Hallan, R I; Williams, N S; Melling, J; Waldron, D J; Womack, N R; Morrison, J F

1988-09-24

In seven patients with anismus the striated sphincter muscle complex was selectively weakened by local injection of Clostridium botulinum type A toxin. Symptom scores improved significantly and correlated with a significant reduction in the maximum voluntary and canal squeeze pressure and a significant increase in the anorectal angle on straining. Botulinum A toxin seems to be promising treatment for some patients with anismus.

Protein Domain Analysis of C. botulinum Type A Neurotoxin and Its Relationship with Other Botulinum Serotypes

OpenAIRE

Sharma, Shashi K.; Basavanna, Uma; Shukla, Hem D.

2009-01-01

Botulinum neurotoxins (BoNTs) are highly potent poisons produced by seven serotypes of Clostridium botulinum. The mechanism of neurotoxin action is a multistep process which leads to the cleavage of one of three different SNARE proteins essential for synaptic vesicle fusion and transmission of the nerve signals to muscles: synaptobrevin, syntaxin, or SNAP-25. In order to understand the precise mechanism of neurotoxin in a host, the domain structure of the neurotoxin was analyzed among differe...

Development of a quail embryo model for the detection of botulinum toxin type A activity

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Clostridium botulinum is a ubiquitous microorganism which under certain anaerobic conditions can produce botulinum toxins. Due to concerns in regards to both food-borne illness and the potential use of botulinum toxin as a biological weapon, the capability to assess the amount of toxin in a food or...

Botulinum toxin in the treatment of refractory vaginismus.

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Ghazizadeh, Shirin; Nikzad, Masoomeh

2004-11-01

To investigate the efficacy of botulinum toxin injection to treat women with moderate and severe vaginismus. Twenty-four women referred to our clinic from February 2002 to February 2004 (mean age 25 years; range 19-34 years) with third- to fourth-degree vaginismus were recruited for this study. These women had previous unsuccessful treatments. Botulinum toxin (150-400 mIU) was injected into the puborectalis muscles in 3 sites on each side of the vagina. Twenty-three patients (95.8%) had vaginal examinations 1 week postoperatively that showed little or no vaginismus, 18 (75%) achieved satisfactory intercourse after the first injection, 4 (16.7%) had mild pain, 1 was cured after a second injection, 1 patient refused vaginal examination and did not attempt to have coitus, and another had no coitus as a result of her husband's secondary impotence. The women were followed up for a mean of 12.3 months (range 2-24 months), and there were no cases of recurrence. In refractory cases of vaginismus when conventional therapies have failed, local injection of botulinum toxin can be considered. III.

Effect of Botulinum Toxin and Surgery among Spasmodic Dysphonia Patients.

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van Esch, Babette F; Wegner, Inge; Stegeman, Inge; Grolman, Wilko

2017-02-01

Objective The effect of botulinum toxin among patients with adductor spasmodic dysphonia (AdSD) is temporary. To optimize long-term treatment outcome, other therapy options should be evaluated. Alternative treatment options for AdSD comprise several surgical treatments, such as thyroarytenoid myotomy, thyroplasty, selective laryngeal adductor denervation-reinnervation, laryngeal nerve crush, and recurrent laryngeal nerve resection. Here, we present the first systematic review comparing the effect of botulinum toxin with surgical treatment among patients diagnosed with AdSD. Data Sources MEDLINE (PubMed), EMBASE, and the Cochrane Library. Methods Articles were reviewed by 2 independent authors, and data were compiled in tables for analysis of the objective outcome (voice expert evaluation after voice recording), the subjective outcome (patient self-assessment scores), and voice-related quality of life (Voice Health Index scores). Results No clinical trials comparing both treatment modalities were identified. Single-armed studies evaluated either the effect of botulinum toxin or surgical treatment. Thirteen studies reported outcomes after botulinum toxin treatment (n = 419), and 9 studies reported outcomes after surgical treatment (n = 585 patients). A positive effect of bilateral botulinum toxin injections was found for the objective voice outcome, subjective voice outcome, and quality of life. The duration of the beneficial effect ranged from 15 to 18 weeks. Surgical treatment had an overall positive effect on objective voice improvement, subjective voice improvement, and quality of live. Conclusion No preference for one treatment could be demonstrated. Prospective clinical trials comparing treatment modalities are recommended to delineate the optimal outcomes by direct comparison.

Contralateral botulinum toxin injection to improve facial asymmetry after acute facial paralysis.

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Kim, Jin

2013-02-01

The application of botulinum toxin to the healthy side of the face in patients with long-standing facial paralysis has been shown to be a minimally invasive technique that improves facial symmetry at rest and during facial motion, but our experience using botulinum toxin therapy for facial sequelae prompted the idea that botulinum toxin might be useful in acute cases of facial paralysis, leading to improve facial asymmetry. In cases in which medical or surgical treatment options are limited because of existing medical problems or advanced age, most patients with acute facial palsy are advised to await spontaneous recovery or are informed that no effective intervention exists. The purpose of this study was to evaluate the effect of botulinum toxin treatment for facial asymmetry in 18 patients after acute facial palsy who could not be optimally treated by medical or surgical management because of severe medical or other problems. From 2009 to 2011, nine patients with Bell's palsy, 5 with herpes zoster oticus and 4 with traumatic facial palsy (10 men and 8 women; age range, 22-82 yr; mean, 50.8 yr) participated in this study. Botulinum toxin A (Botox; Allergan Incorporated, Irvine, CA, USA) was injected using a tuberculin syringe with a 27-gauge needle. The amount injected per site varied from 2.5 to 3 U, and the total dose used per patient was 32 to 68 U (mean, 47.5 +/- 8.4 U). After administration of a single dose of botulinum toxin A on the nonparalyzed side of 18 patients with acute facial paralysis, marked relief of facial asymmetry was observed in 8 patients within 1 month of injection. Decreased facial asymmetry and strengthened facial function on the paralyzed side led to an increased HB and SB grade within 6 months after injection. Use of botulinum toxin after acute facial palsy cases is of great value. Such therapy decreases the relative hyperkinesis contralateral to the paralysis, leading to greater symmetric function. Especially in patients with medical

Treatment of chronic tension-type headache with botulinum toxin: a double-blind, placebo-controlled clinical trial

NARCIS (Netherlands)

Padberg, M.; de Bruijn, S. F. T. M.; de Haan, R. J.; Tavy, D. L. J.

2004-01-01

Botulinum toxin is increasingly advocated as effective treatment in chronic tension-type headache. We conducted a randomized, placebo-controlled clinical trial to prove efficacy of botulinum toxin in chronic tension-type headache. Patients were randomly assigned to receive botulinum toxin (maximum

Botulinum Toxin in Secondarily Nonresponsive Patients with Spasmodic Dysphonia.

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Mor, Niv; Tang, Christopher; Blitzer, Andrew

2016-09-01

Chemodenervation with botulinum toxin (BoNT) has been effective and well tolerated for all types of dystonia for >30 years. We reviewed outcomes of our patients treated with BoNT serotype A (BoNT-A) for spasmodic dysphonia (SD) who became secondarily nonresponsive. We found that 8 of 1400 patients became nonresponsive to BoNT-A (0.57%), which is lower than the secondary nonresponse rate in other dystonias. After a cessation period, 4 of our patients resumed BoNT-A injections, and recurrence of immunoresistance was not seen in any of them. When compared with patients with other dystonias, patients with SD receive extremely low doses of BoNT. Small antigen challenge may explain the lower rate of immunoresistance and long-lasting efficacy after BoNT-A is restarted among secondary nonresponsive patients with SD. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

[Seniority of neurobladder and effectiveness of a first intradetrusor injection of botulinum toxin].

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Lacout, M; Guinet-Lacoste, A; Popoff, M; Verollet, D; Lebreton, F; Amarenco, G

2015-09-01

Intradetrusor injection of botulinum toxin is one of the second-line therapy of neurologenic detrusor overactivity. In 26% to 66% of the cases, intradetrusor injection of botulinum toxin is inefficient in order to reduce overactive bladder symptoms and/or overactive detrusor. The objective of this study is to determine whether it exists a link between the efficacy of the first IDBT and the length of neurological detrusor overactivity symptoms. Retrospective study on 79 patients which have a first intradetrusor injection of botulinum toxin between January 2001 and December 2013. Inclusion criteria were patients older than 18 and having neurological detrusor overactivity. There is no significant difference of intradetrusor injection of botulinum toxin efficacy according to duration of urinary symptoms in the general neurologigal population (multiple sclerosis, spinal cord injury, spinal cord compression, ischemic pathology, infectious pathology) with the mean age being 46 years. On the contrary, the length of evolution of neurological detrusor overactivity symptoms before the intradetrusor botox injection therapy and the efficiency of the first intradetrusor injection of botulinum toxin seem to be correlated with negative results in patients with multiple sclerosis. The duration of urinary symptoms is a predictive factor of primary failure of intradetrusor injection of botulinum toxin in multiple sclerosis patients, in univariate analysis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

BOTULINUM TOXIN FOR THE TREATMENT OF CHRONIC HEADACHE

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L. B. Zavaliy

2015-01-01

Full Text Available ABSTRACT. The article deals with the use of botulinum toxin in the treatment of chronic headache. We present four clinical cases of patients who sought treatment in the “Pain Clinic” of N.V. Sklifosovsky Research Institute for Emergency Medicine with a chronic severe cephalgic syndrome of different genesis (migraine, tension headache, dystonia, which had not responded to outpatient treatment for a long time. The paper shows the change of pain in patients with various forms of headache after treatment with botulinum toxin type A, indicating the effectiveness of the method in these patients. 

Sphincter of Oddi botulinum toxin injection to prevent pancreatic fistula after distal pancreatectomy.

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Hackert, Thilo; Klaiber, Ulla; Hinz, Ulf; Kehayova, Tzveta; Probst, Pascal; Knebel, Phillip; Diener, Markus K; Schneider, Lutz; Strobel, Oliver; Michalski, Christoph W; Ulrich, Alexis; Sauer, Peter; Büchler, Markus W

2017-05-01

Postoperative pancreatic fistula represents the most important complication after distal pancreatectomy. The aim of this study was to evaluate the use of a preoperative endoscopic injection of botulinum toxin into the sphincter of Oddi to prevent postoperative pancreatic fistula (German Clinical Trials Register number: DRKS00007885). This was an investigator-initiated, prospective clinical phase I/II trial with an exploratory study design. We included patients who underwent preoperative endoscopic sphincter botulinum toxin injection (100 units of Botox). End points were the feasibility, safety, and postoperative outcomes, including postoperative pancreatic fistula within 30 days after distal pancreatectomy. Botulinum toxin patients were compared with a control collective of patients undergoing distal pancreatectomy without botulinum toxin injection by case-control matching in a 1:1 ratio. Between February 2015 and February 2016, 29 patients were included. All patients underwent successful sphincter of Oddi botulinum toxin injection within a median of 6 (range 0-10) days before operation. One patient had an asymptomatic, self-limiting (48 hours) increase in serum amylase and lipase after injection. Distal pancreatectomy was performed in 24/29 patients; 5 patients were not resectable. Of the patients receiving botulinum toxin, 7 (29%) had increased amylase levels in drainage fluid on postoperative day 3 (the International Study Group of Pancreatic Surgery definition of postoperative pancreatic fistula grade A) without symptoms or need for reintervention. Importantly, no clinically relevant fistulas (International Study Group of Pancreatic Surgery grades B/C) were observed in botulinum toxin patients compared to 33% postoperative pancreatic fistula grade B/C in case-control patients (P botulinum toxin injection is a novel and safe approach to decrease the incidence of clinically relevant postoperative pancreatic fistula after distal pancreatectomy. The results of

Cost-Effectiveness of Treating Upper Limb Spasticity Due to Stroke with Botulinum Toxin Type A: Results from the Botulinum Toxin for the Upper Limb after Stroke (BoTULS Trial

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Nick Steen

2012-11-01

Full Text Available Stroke imposes significant burdens on health services and society, and as such there is a growing need to assess the cost-effectiveness of stroke treatment to ensure maximum benefit is derived from limited resources. This study compared the cost-effectiveness of treating post-stroke upper limb spasticity with botulinum toxin type A plus an upper limb therapy programme against the therapy programme alone. Data on resource use and health outcomes were prospectively collected for 333 patients with post-stroke upper limb spasticity taking part in a randomized trial and combined to estimate the incremental cost per quality adjusted life year (QALY gained of botulinum toxin type A plus therapy relative to therapy alone. The base case incremental cost-effectiveness ratio (ICER of botulinum toxin type A plus therapy was £93,500 per QALY gained. The probability of botulinum toxin type A plus therapy being cost-effective at the England and Wales cost-effectiveness threshold value of £20,000 per QALY was 0.36. The point estimates of the ICER remained above £20,000 per QALY for a range of sensitivity analyses, and the probability of botulinum toxin type A plus therapy being cost-effective at the threshold value did not exceed 0.39, regardless of the assumptions made.

Vocal aging and adductor spasmodic dysphonia: Response to botulinum toxin injection

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Michael P Cannito

2008-03-01

Full Text Available Michael P Cannito, Joel C Kahane, Lesya ChornaSchool of Audiology and Speech-Language Pathology, The University of Memphis, Memphis, TN, USAAbstract: Aging of the larynx is characterized by involutional changes which alter its biomechanical and neural properties and create a biological environment that is different from younger counterparts. Illustrative anatomical examples are presented. This natural, non-disease process appears to set conditions which may influence the effectiveness of botulinum toxin injection and our expectations for its success. Adductor spasmodic dysphonia, a type of laryngeal dystonia, is typically treated using botulinum toxin injections of the vocal folds in order to suppress adductory muscle spasms which are disruptive to production of speech and voice. A few studies have suggested diminished response to treatment in older patients with adductor spasmodic dysphonia. This retrospective study provides a reanalysis of existing pre-to-post treatment data as function of age. Perceptual judgments of speech produced by 42 patients with ADSD were made by two panels of professional listeners with expertise in voice or fluency of speech. Results demonstrate a markedly reduced positive response to botulinum toxin treatment in the older patients. Perceptual findings are further elucidated by means of acoustic spectrography. Literature on vocal aging is reviewed to provide a specific set of biological mechanisms that best account for the observed interaction of botulinum toxin treatment with advancing age.Keywords: vocal aging, adductor spasmodic dysphonia, botulinum toxin, voice quality, speech fluency

Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature

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Michael W. Peck

2017-01-01

Full Text Available Botulinum neurotoxins are diverse proteins. They are currently represented by at least seven serotypes and more than 40 subtypes. New clostridial strains that produce novel neurotoxin variants are being identified with increasing frequency, which presents challenges when organizing the nomenclature surrounding these neurotoxins. Worldwide, researchers are faced with the possibility that toxins having identical sequences may be given different designations or novel toxins having unique sequences may be given the same designations on publication. In order to minimize these problems, an ad hoc committee consisting of over 20 researchers in the field of botulinum neurotoxin research was convened to discuss the clarification of the issues involved in botulinum neurotoxin nomenclature. This publication presents a historical overview of the issues and provides guidelines for botulinum neurotoxin subtype nomenclature in the future.

Botulinum toxin as a therapeutic agent to prevent relapse in deep bite patients.

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Mücke, Thomas; Löffel, Anja; Kanatas, Anastasios; Karnezi, Sandy; Rana, Majeed; Fichter, Andreas; Haarmann, Stephan; Wolff, Klaus-Dietrich; Loeffelbein, Denys John

2016-05-01

The etiology of deep bite is multifactorial. One of the causes is increased muscular activity. This makes the treatment of deep bite malocclusions difficult and often results in relapse in many cases. In this work we compared patients with surgical orthognathic treatment only and surgical orthognathic treatment with additional injections of botulinum toxin after mandibular advancement for class II division 2 malocclusion. This is a prospective study. Adult patients were assessed pretreatment (T1), posttreatment (T2), and long-term after 1 year (T3). In total, 32 patients (mean age, 30.7 years; 23 women and 9 men) reached the study end point (T3); 24 patients were treated without botulinum toxin and 8 patients received preoperative injections of botulinum toxin. Significant differences between both groups were observed, with a more stable result for the experimental group treated with botulinum toxin. In a selective group of adult patients with a class II division II incisor relationship and with a class II skeletal base, botulinum toxin injections can effectively prevent relapse. This may present an alternative to a conventional myotomy. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Unilateral transient mydriasis and ptosis after botulinum toxin injection for a cosmetic procedure

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Akkaya S

2015-02-01

Full Text Available Sezen Akkaya,1 Hatice Kübra Kökcen,1 Tuğba Atakan2 1Fatih Sultan Mehmet Education and Training Hospital, Ophthalmology Clinics, Bostanci, Istanbul, 2Aksaray Hospital, Ophthalmology Clinics, Konya, Turkey Abstract: We report a case of unilateral transient mydriasis and ptosis after botulinum toxin injection applied by a medical doctor for a cosmetic procedure. A 36-year-old nurse was referred to our eye clinic with unilateral mydriasis and ptosis in the right eye 3 days after botulinum toxin injection for a cosmetic procedure. Botulinum toxin was applied to her eye by a doctor at her hospital who was not an ophthalmologist. She was treated with topical apraclonidine 0.5% ophthalmic solution. Her ptosis decreased to 2 mm with apraclonidine and her visual axis improved. Mydriasis was present for 3 weeks and then disappeared. Mild ptosis continued for 3 months, then resolved completely. Patients seeking treatment with botulinum toxin A for cosmetic purposes should be warned about the possibility of ptosis and mydriasis after injection. If these side effects are seen, the patient must be referred to an ophthalmologist for appropriate management. Keywords: botulinum toxin, mydriasis, ptosis

Effects of X-irradiation on axonal sprouting induced by botulinum toxin

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Gomez, S; Duchen, L W [National Hospital, London (UK); Hornsey, S [Hammersmith Hospital, London (UK). M.R.C. Cyclotron Unit

1982-01-01

The effect of X-irradiation on axonal sprouting of motor nerves induced by botulinum toxin was examined. Muscles of one leg in the mouse were X-irradiated (15Gy) prior to the injection of a locally paralysing dose of botulinum toxin. It was found that axonal sprouting occurred as expected, but the sprouts remained unmyelinated and many degenerated. Fewer new end-plates were formed, muscles remained more severely atrophied and supersensitive to acetylcholine and recovery of neuromuscular transmission was greatly delayed when compared with the effects of botulinum toxin alone. X-irradiation did not prevent sprouting but, probably by impairing Schwann cell proliferation, altered axon-Schwann cell relationships and prevented the maturation of newly-formed axons and the differentiation of new end-plates.

AbobotulinumtoxinA Efficacy and Safety in Children With Equinus Foot Previously Treated With Botulinum Toxin.

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Dabrowski, Edward; Bonikowski, Marcin; Gormley, Mark; Volteau, Magali; Picaut, Philippe; Delgado, Mauricio R

2018-05-01

The effects of botulinum toxin are transient, and repeat injections are required in children with lower-limb spasticity. However, the efficacy of botulinum toxin in patients who have received previous injections has remained largely unexplored. We present subgroup analyses of a phase III study conducted in ambulatory children (aged two to 17) with spastic equinus foot. Patients were randomized to single doses of abobotulinumtoxinA 10 U/kg/leg, 15 U/kg/leg, or placebo injected into the gastrocnemius-soleus complex (one or both legs). The first analysis was prespecified to review the effect of abobotulinumtoxinA in children previously treated with botulinum toxin versus those children new to the treatment; a second post hoc analysis evaluated the effect of abobotulinumtoxinA in children who changed botulinum toxin formulation. Of the 241 randomized patients, 113 had previously received botulinum toxin, including 86 who had been treated with another formulation. In both analyses, muscle tone (Modified Ashworth Scale) and the Physicians Global Assessment, at week 4, improved with abobotulinumtoxinA treatment versus placebo, regardless of baseline botulinum toxin status. Placebo responses in patients new to treatment were consistently higher than in the previously treated group. These results demonstrate similar abobotulinumtoxinA efficacy and safety profiles in children with spasticity who are new to botulinum toxin treatment and those children who were previously treated. The efficacy and safety of abobotulinumtoxinA treatment in these previously treated patients were comparable with the overall trial population, indicating that doses of 10 and 15 U/kg/leg are suitable starting doses for children with spasticity regardless of the previous botulinum toxin preparation used. Copyright © 2018 Elsevier Inc. All rights reserved.

Muscle selection for treatment of cervical dystonia with botulinum toxin : A systematic review

NARCIS (Netherlands)

Nijmeijer, S. W. R.; Koelman, J. H. T. M.; Kamphuis, D. J.; Tijssen, M. A. J.

Rationale: Cervical dystonia, also called spasmodic torticollis, is the most common form of (primary) dystonia. Intramuscular injections with botulinum toxin are the first line of treatment for cervical dystonia. To optimise the treatment response to botulinum toxin correct muscles should be

Muscle selection for treatment of cervical dystonia with botulinum toxin - A systematic review

NARCIS (Netherlands)

Nijmeijer, S. W. R.; Koelman, J. H. T. M.; Kamphuis, D. J.; Tijssen, M. A. J.

2012-01-01

Rationale: Cervical dystonia, also called spasmodic torticollis, is the most common form of (primary) dystonia. Intramuscular injections with botulinum toxin are the first line of treatment for cervical dystonia. To optimise the treatment response to botulinum toxin correct muscles should be

The innovative therapeutic application of botulinum toxin type A in urology patients

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Chrysoula Belai

2016-06-01

Full Text Available In the history of medical science the use of botulinum toxin was impressive. In the early 18th century it was defined as the neurotoxin implicated in the deadly disease botulism. Today, despite the toxic action finds application in the treatment of various diseases in a wide range of Medicine. Its use in urology was revolutionary in the treatment of neurogenic bladder, refractory idiopathic detrusor overactivity and other painful syndromes. The purpose of this review was to describe the treatment option of intravesical injection of botulinum toxin, in diseases of the urinary tract. The review showed that after many test applications under the experimental studies, the botulinum toxin type A has already established itself as the new treatment of choice after failure of conservative drug dealing in patients with neuro-urological symptoms of lower urinary tract. Cases of application of botulinum toxin in Urology are related to overactive bladder, neurogenic or idiopathic etiology, as bladder pain syndrome and chronic pelvic pain syndrome. According to the guidelines of the European Union directives Urology, the intravesical botulinum toxin injections are the most effective, minimally invasive treatment which results in reducing neurogenic hyperactivity of detrusor. In conclusion, this is a safe, easy and effective method that can be applied by health professionals, helping improve patients’ quality of life with neuro-urological diseases.

Botulinum toxin therapy in Frey's syndrome: a retrospective study of 440 treatments in 100 patients.

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Jansen, S; Jerowski, M; Ludwig, L; Fischer-Krall, E; Beutner, D; Grosheva, M

2017-04-01

Frey's syndrome is characterised as sweating, redness and warmth of the parotideal area and is often treated with botulinum toxin A. The objective of this retrospective study was to prove whether the toxin dosage and time-to-treatment intervals change after repeated botulinum toxin injections. The charts of patients, who were treated for Frey's syndrome during the last 16 years, were assessed. Three brands of botulinum toxin A were available for therapy. The Minor test was used to confirm the sweating before each treatment and to determine the toxin dosage. Constant amount of botulinum toxin was injected per cm 2 of the affected area. Patients consulted our department for the next treatment as soon as they felt disturbed by recurring sweating and when the sweating was objectively evident in the Minor test. Time intervals between treatments and injected toxin dosages were assessed. In total, 100 patients received 440 treatments in 16 years. Repeated injections, median 4.0, were carried out in 70.5% of patients. Median time interval to the first injection was 2.8 years. Median time interval between treatments was 12.0 months and showed to be steady (anova, P = .49, F = 1.01). Duration of effect of botulinum toxin on Frey's syndrome was long-lasting and stable with no significantly different time intervals between treatments. The extent of the sweating area did not vary significantly after repeated treatments and required a constant dose of botulinum toxin A. © 2016 John Wiley & Sons Ltd.

Effectiveness of botulinum toxin A in treatment of refractory erythromelalgia

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Kuan-Hsiang Lin

2013-05-01

Full Text Available Erythromelalgia is characterized by intense burning pain, erythema, and heat in affected areas after precipitating factors such as warm temperature or stress. It is refractory to treatment in some situations. We describe a woman with adenosquamous cell carcinoma of the lung and medically refractory erythromelalgia. The symptoms of erythromelalgia presented as refractory to any medical treatment. Due to the unresponsive nature of her condition, botulinum toxin type A (onabotulinumtoxin A was injected over both of her cheeks, periodically for six cycles. Her symptoms responded dramatically to subcutaneous and intradermal injection of botulinum toxin type A. Repetitive injection demonstrated consistent and reproducible responses, and the efficacy was maintained for approximately 1 month. No adverse effects or complications were noted. Botulinum toxin type A might be safe and effective as an alternative treatment for refractory erythromelalgia, but further large-scale studies are required.

The Efficacy of Botulinum Toxin A Intramuscular Injections in After-Stroke Spasticity

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Melek Karaçam

2010-09-01

Full Text Available OBJECTIVE: Spasticity is a common dysfunction in stroke patients. It hinders the performance of everyday living activities and lowers the quality of life. In this study, it was aimed to investigate the effects of botulinum toxin A therapy on various aspects, such as muscle tone, pain, daily living activities and disability. METHODS: Fifteen patients with stroke presenting with focal spasticity in the botulinum toxin outpatient unit were evaluated. Results before and after treatment were evaluated by applying different scales. Modified Ashworth Scale was applied for the severity of spasticity. The Medical Council Research Scale was used to test muscle power, and the disability scoring scale, Visual Analogue Pain Scale and Barthel index were the other measures tested. RESULTS: It was found that therapy with botulinum toxin A was effective in spasticity. The increased muscle tone and the disability scores decreased prominently after the treatment (p< 0.05. Lower values in pain scores (p< 0.05 also contributed to better functional outcome (p< 0.01. Along with the significantly good outcome according to the scales, the higher scores in quality of life, feeling of well-being, good performance during the physiotherapy sessions, and less medications needed for spasticity were also indications in commencing the therapy of botulinum toxin A in spasticity. CONCLUSION: Spasticity is a complicated condition causing serious disability. Botulinum toxin A is a preferred therapy when there is an increased motor activity. The effects of the agent are reversible and reliable. The duration of the treatment is long-lasting. Since botulinum toxin A is easily applied and the outcome in focal spasticity is favorable, it is recommended as the first-line choice in the treatment of focal spasticity

Treatment of displaced mandibular condylar fracture with botulinum toxin A.

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Akbay, Ercan; Cevik, Cengiz; Damlar, Ibrahim; Altan, Ahmet

2014-04-01

The aim of this case report is to discuss the effect on condylar reduction of botulinum toxin A treatment used in a child with displaced fracture at condylar neck of mandible. A 3-years old boy was admitted to our clinic for incomplete fracture of mandibular symphysis and displaced condylar fracture at the left side. An asymmetrical occlusal splint with intermaxillary fixation was used instead of open reduction and internal fixation because of incomplete fracture of symphysis and possible complications of condyle surgery. However, it was observed that condylar angulation persisted despite this procedure. Thus, botulinum toxin A was administered to masseter, temporalis and pterygoideus medialis muscles. At the end of first month, it was seen that mandibular condyle was almost completely recovered and that fusion was achieved. In conclusion, Botulinum A toxin injection aiming the suppression of masticatory muscle strength facilitates the reduction in the conservative management of displaced condyle in pediatric patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Botulinum Toxin in Management of Limb Tremor

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Elina Zakin

2017-11-01

Full Text Available Essential tremor is characterized by persistent, usually bilateral and symmetric, postural or kinetic activation of agonist and antagonist muscles involving either the distal or proximal upper extremity. Quality of life is often affected and one’s ability to perform daily tasks becomes impaired. Oral therapies, including propranolol and primidone, can be effective in the management of essential tremor, although adverse effects can limit their use and about 50% of individuals lack response to oral pharmacotherapy. Locally administered botulinum toxin injection has become increasingly useful in the management of essential tremor. Targeting of select muscles with botulinum toxin is an area of active research, and muscle selection has important implications for toxin dosing and functional outcomes. The use of anatomical landmarks with palpation, EMG guidance, electrical stimulation, and ultrasound has been studied as a technique for muscle localization in toxin injection. Earlier studies implemented a standard protocol for the injection of (predominantly wrist flexors and extensors using palpation and EMG guidance. Targeting of muscles by selection of specific activators of tremor (tailored to each patient using kinematic analysis might allow for improvement in efficacy, including functional outcomes. It is this individualized muscle selection and toxin dosing (requiring injection within various sites of a single muscle that has allowed for success in the management of tremors.

Vocal aging and adductor spasmodic dysphonia: Response to botulinum toxin injection

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Cannito, Michael P; Kahane, Joel C; Chorna, Lesya

2008-01-01

Aging of the larynx is characterized by involutional changes which alter its biomechanical and neural properties and create a biological environment that is different from younger counterparts. Illustrative anatomical examples are presented. This natural, non-disease process appears to set conditions which may influence the effectiveness of botulinum toxin injection and our expectations for its success. Adductor spasmodic dysphonia, a type of laryngeal dystonia, is typically treated using botulinum toxin injections of the vocal folds in order to suppress adductory muscle spasms which are disruptive to production of speech and voice. A few studies have suggested diminished response to treatment in older patients with adductor spasmodic dysphonia. This retrospective study provides a reanalysis of existing pre-to-post treatment data as function of age. Perceptual judgments of speech produced by 42 patients with ADSD were made by two panels of professional listeners with expertise in voice or fluency of speech. Results demonstrate a markedly reduced positive response to botulinum toxin treatment in the older patients. Perceptual findings are further elucidated by means of acoustic spectrography. Literature on vocal aging is reviewed to provide a specific set of biological mechanisms that best account for the observed interaction of botulinum toxin treatment with advancing age. PMID:18488884

Vocal aging and adductor spasmodic dysphonia: response to botulinum toxin injection.

Science.gov (United States)

Cannito, Michael P; Kahane, Joel C; Chorna, Lesya

2008-01-01

Aging of the larynx is characterized by involutional changes which alter its biomechanical and neural properties and create a biological environment that is different from younger counterparts. Illustrative anatomical examples are presented. This natural, non-disease process appears to set conditions which may influence the effectiveness of botulinum toxin injection and our expectations for its success. Adductor spasmodic dysphonia, a type of laryngeal dystonia, is typically treated using botulinum toxin injections of the vocal folds in order to suppress adductory muscle spasms which are disruptive to production of speech and voice. A few studies have suggested diminished response to treatment in older patients with adductor spasmodic dysphonia. This retrospective study provides a reanalysis of existing pre-to-post treatment data as function of age. Perceptual judgments of speech produced by 42 patients with ADSD were made by two panels of professional listeners with expertise in voice or fluency of speech. Results demonstrate a markedly reduced positive response to botulinum toxin treatment in the older patients. Perceptual findings are further elucidated by means of acoustic spectrography. Literature on vocal aging is reviewed to provide a specific set of biological mechanisms that best account for the observed interaction of botulinum toxin treatment with advancing age.

Plastic changes in spinal synaptic transmission following botulinum toxin A in patients with post-stroke spasticity.

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Kerzoncuf, Marjorie; Bensoussan, Laurent; Delarque, Alain; Durand, Jacques; Viton, Jean-Michel; Rossi-Durand, Christiane

2015-11-01

The therapeutic effects of intramuscular injections of botulinum toxin-type A on spasticity can largely be explained by its blocking action at the neuromuscular junction. Botulinum toxin-type A is also thought to have a central action on the functional organization of the central nervous system. This study assessed the action of botulinum toxin-type A on spinal motor networks by investigating post-activation depression of the soleus H-reflex in post-stroke patients. Post-activation depression, a presynaptic mechanism controlling the synaptic efficacy of Ia-motoneuron transmission, is involved in the pathophysiology of spasticity. Eight patients with chronic hemiplegia post-stroke presenting with lower limb spasticity and requiring botulinum toxin-type A injection in the ankle extensor muscle. Post-activation depression of soleus H-reflex assessed as frequency-related depression of H-reflex was investigated before and 3, 6 and 12 weeks after botulinum toxin-type A injections in the triceps surae. Post-activation depression was quantified as the ratio between H-reflex amplitude at 0.5 and 0.1 Hz. Post-activation depression of soleus H-reflex, which is reduced on the paretic leg, was affected 3 weeks after botulinum toxin-type A injection. Depending on the residual motor capacity of the post-stroke patients, post-activation depression was either restored in patients with preserved voluntary motor control or further reduced in patients with no residual voluntary control. Botulinum toxin treatment induces synaptic plasticity at the Ia-motoneuron synapse in post-stroke paretic patients, which suggests that the effectiveness of botulinum toxin-type A in post-stroke rehabilitation might be partly due to its central effects.

Endocardial botulinum toxin injection into ganglionated plexi in order to reduce atrial fibrillation inducibility

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А. Г. Стрельников

2016-01-01

Full Text Available Objective. Prior animal studies suggest that botulinum toxin injection into the epicardial fat pads can suppress atrial fibrillation (AF inducibility. The purpose of the present study was to assess the efficacy and safety of endocardial botulinum toxin injection into epicardial fat pads and intramyocardial left atrial ganglionated plexi (GP for preventing AF.Methods. Twenty-four dogs were separated into 3 groups: endocardial approach for botulinum toxin (Xeomin, Germany injection into epicardial fat pads and intramyocardial GPs; endocardial approach for placebo injection (0.9% normal saline; control 1; n = 8 and epicardial approach for botulinum toxin injection (control 2; n = 8.Results. A mean of 6.9±1.7 intramyocardial injections (10 U/0.2 mL at each and 3 injections (50 U/1 mL at each were administered into each site exhibiting a positive vagal response and into each epicardial fat pad in all groups (p>0.05 between groups.The injections of botulinum toxin demonstrated dramatic prolongation of ERP in all PV-atrial junctions. This effect correlated with less pronounced ERP shortening in response to vagal nerve stimulation. Suppression of AF inducibility was observed at 7 days after endocardial botulinum toxin injections. The level of AF inducibility was: at 7 days – 57% (p<0.001 vs placebo; p<0.001 vs baseline; at 14 days – 61% (p<0.001 vs placebo; p<0.001 vs baseline; at 1 month – 38% (p<0.001 vs placebo; p<0.001 vs baseline; at 3 months – 23% (p = 0.003; p = 0.06 vs baseline. There were no differences between botulinum groups (p>0.05 for all. The effect of AF suppression disappeared at 3 months. No procedure-related complications occurred.Conclusion. Botulinum toxin injection into intramyocardial GPs and epicardial fat pads by an endocardial approach is feasible and safe. It provides complete removal of cardiac vagal responses and reliably reduces vulnerability to atrial fibrillation.

Botulinum toxin for treatment of Frey's syndrome: report of two cases

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Teive Hélio A.G.

2003-01-01

Full Text Available Frey's syndrome is a phenomenon of hemifacial flushing and sweating after gustatory stimulus, usually secondary to surgical trauma over the parotid gland, although other injury mechanisms may be seen. It is accepted as a result of aberrant regeneration of facial autonomic nerve fibers. Treatment evolved from ineffective medical and surgical approaches to botulinum toxin. We evaluate the effectiveness and safety of botulinum toxin in the treatment of this complication in two patients.

Retargeting the Clostridium botulinum C2 toxin to the neuronal cytosol.

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Pavlik, Benjamin J; Hruska, Elizabeth J; Van Cott, Kevin E; Blum, Paul H

2016-03-30

Many biological toxins are known to attack specific cell types, delivering their enzymatic payloads to the cytosol. This process can be manipulated by molecular engineering of chimeric toxins. Using toxins with naturally unlinked components as a starting point is advantageous because it allows for the development of payloads separately from the binding/translocation components. Here the Clostridium botulinum C2 binding/translocation domain was retargeted to neural cell populations by deleting its non-specific binding domain and replacing it with a C. botulinum neurotoxin binding domain. This fusion protein was used to deliver fluorescently labeled payloads to Neuro-2a cells. Intracellular delivery was quantified by flow cytometry and found to be dependent on artificial enrichment of cells with the polysialoganglioside receptor GT1b. Visualization by confocal microscopy showed a dissociation of payloads from the early endosome indicating translocation of the chimeric toxin. The natural Clostridium botulinum C2 toxin was then delivered to human glioblastoma A172 and synchronized HeLa cells. In the presence of the fusion protein, native cytosolic enzymatic activity of the enzyme was observed and found to be GT1b-dependent. This retargeted toxin may enable delivery of therapeutics to peripheral neurons and be of use in addressing experimental questions about neural physiology.

In-Vivo Neutralization of Botulinum Neurotoxin Serotype E Using Rabbit Polyclonal Antibody Developed against BoNT/E Light Chain.

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Rani, Sarita; Ponmariappan, S; Sharma, Arti; Kamboj, D V; Jain, A K

2017-01-01

Clostridium botulinum is an obligate anaerobic, Gram positive bacterium that secretes extremely toxic substances known as botulinum neurotoxins (BoNTs) that cause serious paralytic illness called botulism. Based upon the serological properties, these neurotoxin have been classified into seven serotypes designated from A to G. Due to extreme toxicity of BoNTs, these neurotoxins have been designated as category A biowarfare agents. There is no commercial neutralizing antibody available for the treatment of botulism. Hence there is an urgent need to develop therapeutic intervention for prevention and cure of botulism within short period. BoNT antiserum injection is still the effective treatment. In the present study, the recombinant light chain of BoNT/E was successfully purified in soluble form. The purified rBoNT/E LC was used for the generation of polyclonal antibody in rabbit. In order to find out the neutralizing capacity of generated antisera, rabbit antiserum was incubated with 20 LD50 of botulinum neurotoxin type E for 1 hour at 37°C and then injected intraperitoneally (IP) into mice. Further in another set of experiments antiserum was administered in different ways that included administration of - antiserum and BoNT/E toxin simultaneously without preincubation, one after another at the same and different time points for its therapeutic ability. To find out cross neutralization capacity, rBoNT/E LC antiserum was pre-incubated with 5 LD50 of BoNT/A, BoNT/B, BoNT/F and then injected (IP) into mice. In all the cases mice were observed continuously for 96 hours. The results clearly indicate that developed polyclonal rabbit antiserum showed serotype specific neutralization of BoNT/E toxin only but not of BoNT/A, BoNT/B and BoNT/F. The developed antibodies will be used for preventive and therapeutic intervention of type 'E' botulism. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Drooling in Parkinson's disease: A randomized controlled trial of incobotulinum toxin A and meta-analysis of Botulinum toxins.

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Narayanaswami, Pushpa; Geisbush, Thomas; Tarulli, Andrew; Raynor, Elizabeth; Gautam, Shiva; Tarsy, Daniel; Gronseth, Gary

2016-09-01

Botulinum toxins are a therapeutic option for drooling in Parkinson's Disease (PD). The aims of this study were to: 1. evaluate the efficacy of incobotulinum toxin A for drooling in PD. 2. Perform a meta-analysis of studies of Botulinum toxins for drooling in PD. 1. Primary study: Randomized, double blind, placebo controlled, cross over trial. Incobotulinum toxin (100 units) or saline was injected into the parotid (20 units) and submandibular (30 units) glands. Subjects returned monthly for three evaluations after each injection. Outcome measures were saliva weight and Drooling Frequency and Severity Scale. 2. Systematic review of literature, followed by inverse variance meta-analyses using random effects models. 1. Primary Study: Nine of 10 subjects completed both arms. There was no significant change in the primary outcome of saliva weight one month after injection in the treatment period compared to placebo period (mean difference, gm ± SD: -0.194 ± 0.61, range: -1.28 to 0.97, 95% CI -0.71 to 0.32). Secondary outcomes also did not change. 2. Meta-analysis of six studies demonstrated significant benefit of Botulinum toxin on functional outcomes (effect size, Cohen's d: -1.32, CI -1.86 to -0.78). The other studies used a higher dose of Botulinum toxin A into the parotid glands. This study did not demonstrate efficacy of incobotulinum toxin A for drooling in PD, but lacked precision to exclude moderate benefit. The parotid/submandibular dose-ratio may have influenced results. Studies evaluating higher doses of incobotulinum toxin A into the parotid glands may be useful. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Contribution of botulinum toxin to maxillo-facial surgery].

Science.gov (United States)

Batifol, D; de Boutray, M; Goudot, P; Lorenzo, S

2013-04-01

Botulinum toxin has a wide range of use in maxillo-facial surgery due to its action on muscles, on the glandular system, and against pain. It already has been given several market authorizations as indicated for: blepharospasm, spasmodic stiff neck, and glabellar lines. Furthermore, several studies are ongoing to prove its effectiveness and usefulness for many other pathologies: treatment of pain following cervical spine surgery; action on salivary glands after trauma, hypertrophy, or hyper-salivation; analgesic action (acknowledged but still being experimented) on neuralgia, articular pain, and keloids scars due to its anti-inflammatory properties. Botulinum toxin injections in the cervico-facial area are more and more used and should be to be correctly assessed. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Pneumothorax complicating botulinum toxin injection in the body of a dilated oesophagus in achalasia

NARCIS (Netherlands)

Weusten, Bas L. A. M.; Samsom, Melvin; Smout, André J. P. M.

2003-01-01

Botulinum toxin is used for an increasing number of indications in the field of gastroenterology. We report a case in which injection of botulinum toxin in the dilated tubular oesophagus in a patient with achalasia was complicated by a pneumothorax necessitating suction drainage

Botulinum toxin in the management of sialorrhoea in acquired brain injury

LENUS (Irish Health Repository)

Carroll, A

2016-06-01

Sialorrhoea as a consequence of severe acquired brain injury can significantly negatively impact on quality of life. Medications used in its management have many side effects which can cause problems in the severely disabled. Botulinum toxin is an effective treatment of sialorrhoea in a number of neurological conditions but may also have a role to play in the management of sialorrhoea following severe ABI. We report on 4 cases of sialorrhoea following acquired brain injury causing a variety of problems, whose parotid glands were injected with Botulinum toxin type A (Dysport) 50mu each, under ultrasound guidance. All cases had a clinically and statistically significant reduction in drooling as measured by the teacher drooling scale (p=0.005) and carers Visual Analogue Scale (p=0.012). There were no side effects reported. Botulinum toxin is an effective treatment for sialorrhoea associated with acquired brain injury.

Long-term outcomes of Botulinum toxin in the treatment of chronic anal fissure: 5 years of follow-up.

Science.gov (United States)

Barbeiro, Sandra; Atalaia-Martins, Catarina; Marcos, Pedro; Gonçalves, Cláudia; Canhoto, Manuela; Arroja, Bruno; Silva, Filipe; Cotrim, Isabel; Eliseu, Liliana; Santos, Antonieta; Vasconcelos, Helena

2017-03-01

Chronic anal fissure is a frequent and disabling disease, often affecting young adults. Botulinum toxin and lateral internal sphincterotomy are the main therapeutic options for refractory cases. Botulinum toxin is minimally invasive and safer compared with surgery, which carries a difficult post-operative recovery and fecal incontinence risk. The long-term efficacy of Botulinum toxin is not well known. The aim of this study was to evaluate the long-term efficacy and safety of Botulinum toxin in the treatment of chronic anal fissure. This was a retrospective study at a single center, including patients treated with Botulinum toxin from 2005 to 2010, followed over at least a period of 5 years. All patients were treated with injection of 25U of Botulinum toxin in the intersphincteric groove. The response was registered as complete, partial, refractory and relapse. Botulinum toxin was administered to 126 patients, 69.8% ( n  = 88) were followed over a period of 5 years. After 3 months, 46.6% ( n  = 41) had complete response, 23.9% ( n  = 21) had partial response and 29.5% ( n  = 26) were refractory. Relapse was observed in 1.2% ( n  = 1) at 6 months, 11.4% ( n  = 10) at 1 year, 2.3% ( n  = 2) at 3 years; no relapse at 5 years. The overall success rate was 64.8% at 5 years of follow-up. Botulinum toxin was well tolerated by all patients and there were no complications. The use of Botulinum toxin to treat patients with chronic anal fissure was safe and effective in long-term follow-up.

Treatment diary for botulinum toxin spasticity treatment

DEFF Research Database (Denmark)

Biering-Sørensen, Bo; Iversen, Helle K; Frederiksen, Inge M S

2017-01-01

The aim of this study is to develop a treatment diary for patients receiving spasticity treatment including botulinum toxin injection and physiotherapy and/or occupational therapy. The diary focuses on problems triggered by skeletal muscle overactivity; agreed goals for treatment and the patient...

Improved soluble expression and characterization of the Hc domain of Clostridium botulinum neurotoxin serotype A in Escherichia coli by using a PCR-synthesized gene and a Trx co-expression strain.

Science.gov (United States)

Chen, Rongchang; Shi, Jing; Cai, Kun; Tu, Wei; Hou, Xiaojun; Liu, Hao; Xiao, Le; Wang, Qin; Tang, Yunming; Wang, Hui

2010-05-01

Botulinum neurotoxin serotype A (BoNT/A) is an extremely potent bacterial protein toxin. The Hc fragment of BoNT/A (AHc) was shown to be non-toxic, antigenic, and capable of eliciting a protective immunity in animals challenged with homologous BoNT. In this study, we synthesized AHc gene by using T4 DNA ligase and PCR. The AHc was expressed at a high level in Escherichia coli successfully. Because of using the Trx co-expression strain, the expressed AHc is in a soluble and active form. The yield of the purified AHc was about 70mg/L, and its purity was up to 90% through one-step affinity chromatography. The AHc was positively identified by the antibodies raised against BoNT/A using immunological-dot-blot and Western blot assays. AHc was shown to bind with gangliosides and elicit immunity against BoNT/A, indicating that the expressed and purified AHc protein retains a functionally active conformation. Furthermore, the purified AHc has a strong immunogenicity and can be used as a potential subunit candidate vaccine for botulinum toxin serotype A. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Safety and efficacy of botulinum toxin injection therapy for esophageal achalasia in Japan.

Science.gov (United States)

Yamaguchi, Daisuke; Tsuruoka, Nanae; Sakata, Yasuhisa; Shimoda, Ryo; Fujimoto, Kazuma; Iwakiri, Ryuichi

2015-11-01

Botulinum toxin injection is an accepted treatment modality for esophageal achalasia in western countries. This pilot study aimed to clarify the effectiveness of botulinum toxin injection for esophageal achalasia in Japanese patients. We enrolled 10 patients diagnosed with esophageal achalasia between 2008 and 2014. A total of 100 U botulinum toxin A was divided into eight aliquots and injected around the esophagogastric junction. We compared the lower esophageal sphincter pressure before and 1 week after treatment. Scores of subjective symptoms for esophageal achalasia were assessed using a visual analog scale (VAS) before and after 1 week of follow-up of treatment. Barium passage was improved in barium esophagography and passage of contrast agent was also improved. Mean Eckardt score was reduced from 5.5 to 1.6 after treatment (ptreatment (p = 0.002). One week after treatment, mean VAS score was reduced from 10 to 3.9 (pachalasia was safe and effective with few complications. Therefore, botulinum toxin could be used as minimally invasive therapy for esophageal achalasia in Japan.

A Beautician’s Dystonia: Long-Lasting Effect of Botulinum Toxin

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Siria Di Martino

2014-01-01

Full Text Available Treatment options for dystonia are not curative but symptomatic; the treatment of choice for focal dystonias is repeated botulinum toxin injections. Here, we present the case of a 46-year-old beautician with focal dystonia in her left hand that affected her ability to work. Pharmacological treatment with clonazepam and gabapentin failed to resolve her symptoms and was discontinued due to side effects (sleepiness, gastrointestinal disorders. Intramuscular injection of botulinum toxin (incobotulinumtoxinA, Xeomin into the extensor digitorum communis (35 U, flexor carpi radialis (35 U, and flexor digitorum superficialis (30 U muscles resulted in complete resolution of symptoms at clinical assessments at 1, 3, 6, and 10 months after the injections, confirmed by the results of surface electromyography 10 months after treatment. The patient was able to work again 1 month after treatment. No reinjection has been necessary at the last evaluation (12 months after treatment. In conclusion, botulinum toxin is an effective treatment for focal dystonia that can have long-lasting effects and can improve patients’ ability to work and quality of life.

Intralesional botulinum toxin-A injection for the treatment of multiple eccrine hidrocystomas.

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Gheisari, Mehdi; Hamedani, Behnaz; Robati, RezaM; Mozafari, Nikoo

2018-01-31

Multiple eccrine hidrocystomas (MEH) are benign cystic lesions of the sweat gland ducts. They are characterized by translucent, skin-colored or bluish dome-shaped papules on the face, causing cosmetic concern. Recently, botulinum toxin-A, because of its antiperspirant properties, has been used to treat facial MEH. However, there are only some case reports in the literature. Here, we conducted a prospective study to assess the efficacy and safety of intralesional injection of botulinum toxin-A (Dysport) for the treatment of MEH. Twenty patients (3 men and 17 women), aged from 31 to 75 years old, participated in this study. A 300 unit vial of botulinum toxin-A (Dysport, Ipsenn Biopharm, United Kingdom) was diluted with 4 ml of saline solution without preservative to achieve a concentration of 7.5U/.1 ml. Up to 1.5 unit of botulinum toxin was injected intradermally at the base of each lesion to raise a visible wheal. The patients were evaluated 7 days later, and any clinical changes or adverse effects were recorded. In all patients, more than 75% of eccrine hidrocystoma lesions resolved without any scaring. The result sustained for 2-5 months. In two patients mild smile asymmetry and in one patient lagophthalmos were noted approximately 5-7 days after injection that gradually resolved in 3 weeks. Intralesional botulinum toxin-A for treatment of multiple hidrocystomas is a simple and well-tolerated procedure. It is accompanied by excellent results, a good postoperative course, and no risk of scarring. It can be considered in patients who did not respond to other treatment or even as the first line therapy.

Botulinum Toxin for the Treatment of Tremor and Tics.

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Lotia, Mitesh; Jankovic, Joseph

2016-02-01

The therapeutic applications of botulinum toxin (BoNT) have grown manifold since its initial approval in 1989 by the U.S. Food and Drug Administration for the treatment of strabismus, blepharospasm, and other facial spasms. Although it is the most potent biologic toxin known to man, long-term studies have established its safety in the treatment of a variety of neurologic and nonneurologic disorders. Despite a paucity of randomized controlled trials, BoNT has been found to be beneficial in treating a variety of tremors and tics when used by clinicians skilled in the administration of the drug for these hyperkinetic movement disorders. Botulinum toxin injections can provide meaningful improvement in patients with localized tremors and tics; in some cases, they may be an alternative to other treatments with more undesirable adverse effects. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Effect of Botulinum Toxin Type A on TGF-β/Smad Pathway Signaling: Implications for Silicone-Induced Capsule Formation.

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Kim, Sena; Ahn, Moonsang; Piao, Yibo; Ha, Yooseok; Choi, Dae-Kyoung; Yi, Min-Hee; Shin, Nara; Kim, Dong Woon; Oh, Sang-Ha

2016-11-01

One of the most serious complications of breast surgery using implants is capsular contracture. Several preventive treatments have been introduced; however, the mechanism of capsule formation has not been resolved completely. The authors previously identified negative effects of botulinum toxin type A on capsule formation, expression of transforming growth factor (TGF)-β1, and differentiation of fibroblasts into myofibroblasts. Thus, the authors investigated how to prevent capsule formation by using botulinum toxin type A, particularly by means of TGF-β1 signaling, in human fibroblasts. In vitro, cultured human fibroblasts were treated with TGF-β1 and/or botulinum toxin type A. Expression of collagen, matrix metalloproteinase, and Smad was examined by Western blotting. The activation of matrix metalloproteinase was observed by gelatin zymography. In vivo, the effect of botulinum toxin type A on the phosphorylation of Smad2 in silicone-induced capsule formation was evaluated by immunocytochemistry. In vitro, the phosphorylation of Smad2 was inhibited by botulinum toxin type A treatment. The expression levels of collagen types 1 and 3 were inhibited by botulinum toxin type A treatment, whereas those of matrix metalloproteinase-2 and matrix metalloproteinase-9 were enhanced. Gelatin zymography experiments confirmed enhanced matrix metalloproteinase-2 activity in collagen degradation. In vivo, botulinum toxin type A treatment reduced capsule thickness and Smad2 phosphorylation in silicone-induced capsules. This study suggests that botulinum toxin type A plays an important role in the inhibition of capsule formation through the TGF-β/Smad signaling pathway. Therapeutic, V.

[Botulinum toxin and rejuvenation of the eye].

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Volpei, Ch; Miniconi, M-J; Brunner, C I; Besins, T; Braccini, F

2013-01-01

Treatments with botulinum toxin in the forehead and periorbital areas may induce disappointing or even paradoxical results. Our study, focused on this area aimed at refining injection techniques by analyzing muscular balances and comparing the effect according to injection doses and topography. This experimental study has been carried out in the form of 2 session workshops, with volunteers duly informed of the study contents and giving their informed consent. It was conducted by physicians and surgeons members of SAMCEP* (Société Avancée de Médecine et Chirurgie Esthétique et Plastique). The botulinum toxin was onabotulinumtoxin A. Results were evaluated 15 days after treatment, in regard to global eyebrow position, eyebrow head and tail position; muscle interactions; lines above the eyebrow. Eleven case reports and their results are shown and discussed. Our study underlines two important insights: muscle balances and "border areas", between orbicularis oculi and corrugator, key features for eyebrow head, and between frontalis and orbicularis oculifor eyebrow tail.

Review of botulinum toxin type A for the prophylactic treatment of chronic daily headache

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Stefan Evers

2007-05-01

Full Text Available Stefan EversDepartment of Neurology, University of Münster, Münster, GermanyAbstract: Botulinum toxin A is increasingly used in the treatment of idiopathic and symptomatic headache disorders. However, only few controlled trials are available and many trials can hardly be compared to each other because of different endpoints and different trial designs. In particular chronic daily headache, which is defined as an idiopathic headache occurring on more than 15 days per month for at least 3 months and a daily duration of at least 4 hours, is considered as a headache disorder with possible efficacy of botulinum toxin A. For the prophylactic treatment of chronic tension-type headache and chronic migraine, no sufficient positive evidence for a successful treatment can be obtained from randomized, double-blind, and placebo-controlled trials to date. For the treatment of chronic daily headache including medication overuse headache, there is some positive evidence for efficacy in a subgroup of patients. To date, the majority of double-blind and placebo-controlled studies do not suggest that botulinum toxin A is efficacious in the treatment of chronic idiopathic headache disorders. However, it is possible that some subgroups of patients with chronic daily headache will benefit from a long-term treatment with botulinum toxin A.Keywords: botulinum toxin A, chronic daily headache, chronic tension-type headache, chronic migraine

Attempts to identify Clostridium botulinum toxin in milk from three experimentally intoxicated Holstein cows

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Moeller, R.B.; Puschner, B.; Walker, R.L.; Rocke, T.E.; Smith, S.R.; Cullor, J.S.; Ardans, A.A.

2009-01-01

Three adult lactating Holstein cows were injected in the subcutaneous abdominal vein with 175 ng/kg of body weight of Clostridium botulinum type C toxin (451 cow median toxic doses) to determine if this botulinum toxin crosses the blood–milk barrier. Whole blood (in sodium heparin) and clotted blood serum samples were taken at 0 min, 10 min, and 3, 6, 9, and 12 h postinoculation. Milk samples were taken at 0 min and at 3, 6, 9 and 12 h postinoculation. All samples were tested for the presence of the toxin using the mouse bioassay and immunostick ELISA test. The immunostick ELISA identified the toxin in whole blood and the mouse bioassay identified the toxin in serum at all times examined in all 3 animals. Toxin was not identified by either detection method in milk samples collected from the 3 animals. From these results, it appears that Clostridium botulinum type C toxin does not cross from the blood to the milk in detectable concentrations.

Effects of botulinum toxin on strength-duration properties.

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Yerdelen, Deniz; Koc, Filiz; Sarica, Yakup

2007-10-01

Axonal excitability studies have been used in several diseases to investigate the underlying pathophysiology. The threshold tracking technique was developed to measure noninvasively several indices of axonal excitability, such as strength-duration properties. This study investigated the possible effects of botulinum toxin on strength-duration time constant (SDTC) in patients with the symptoms and signs of botulism. The clinical and electrophysiological findings of 13 patients who were admitted to the authors' clinic with botulism signs and symptoms were evaluated in a 5-day period after exposure to the toxin prospectively. After routine diagnostic electroneuromyographic examinations and electromyogram with repetitive nerve stimulation at 20-50 Hz, SDTC was studied. The results were compared with 13 age- and sex-matched healthy volunteers. The SDTCs were 381 +/- 60 micros and 471 +/- 84 micros in patients and controls, respectively. There was a statistical difference between the two groups (p = .003, Mann Whitney U test). These findings suggest a possible effect of botulinum toxin, known to be effective at neuromuscular junction, on Na(+)/K(+) pump activity, and Na(+) or K(+) conductance.

Cellular Entry of Clostridium perfringens Iota-Toxin and Clostridium botulinum C2 Toxin.

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Takehara, Masaya; Takagishi, Teruhisa; Seike, Soshi; Oda, Masataka; Sakaguchi, Yoshihiko; Hisatsune, Junzo; Ochi, Sadayuki; Kobayashi, Keiko; Nagahama, Masahiro

2017-08-11

Clostridium perfringens iota-toxin and Clostridium botulinum C2 toxin are composed of two non-linked proteins, one being the enzymatic component and the other being the binding/translocation component. These latter components recognize specific receptors and oligomerize in plasma membrane lipid-rafts, mediating the uptake of the enzymatic component into the cytosol. Enzymatic components induce actin cytoskeleton disorganization through the ADP-ribosylation of actin and are responsible for cell rounding and death. This review focuses upon the recent advances in cellular internalization of clostridial binary toxins.

Clostridium botulinum Spores Found in Honey from Small Apiaries in Poland

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Wojtacka Joanna

2016-12-01

Full Text Available A total of 102 honey samples collected from small apiaries (≤ 20 hives in Poland were analysed for the presence of Clostridium botulinum spores. The samples were prepared using the dilution centrifugation method and cultured in parallel in cooked meat medium (CMM and tripticase peptone glucose yeast (TPGY enrichment broths. Identification of toxin types A, B, and E of Clostridium botulinum strains was performed with the use of the multiplex PCR method. Positive samples were also subjected to quantitative analysis with the use of Clostridium botulinum Isolation Agar Base (CBAB. The prevalence analysis showed 22 (21.6% samples contaminated with C. botulinum spores. The major serotype detected was botulin neurotoxin type A – 16 (72.7% whereas type B was found in 3 (13.6% honey samples and type E also only in 3 (13.6% honey samples. Dual-toxin-producing strains were noted. The average quantity of spores in PCR - C. botulinum positive samples was 190 in 1 gram of honey.

Study on potential Clostridium botulinum growth and toxin production in Parma ham

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Giuseppe Merialdi

2016-04-01

Full Text Available The objective of this study was to investigate Clostridium botulinum growth and toxin production in the industrially manufactured Italian Parma ham. The study focuses on the Parma ham production phase identified as maximum risk to C. botulinum proliferation, i.e. the transition from cold phase (salting and resting to a phase carried out at temperature between 15 and 23°C (drying. A preliminary in vitro test was carried out in order to verify the capability of 6 C. botulinum strains (1 type A, 4 type B, and 1 type E strains to grow in conditions of temperature, pH and NaCl concentration comparable to those of the beginning stage of ham drying. Five C. botulinum strains grew at 20°C and pH 6, four strains produced toxin when inoculated at a concentration equal to 103 cfu/mL at NaCl concentration of 4%, while when the inoculum concentration was 10 cfu/mL, NaCl concentration of 3% resulted the toxin-genesis limiting factor. An experimental contamination with a mixture of the 5 C. botulinum strains selected by the preliminary in vitro test was performed on 9 thighs inoculated at the end of the resting phase. The study was designed to evaluate the potential growth and toxin production in extremely favourable conditions for the bacterium. Type B proteolytic C. botulinum toxin was produced after 14 days of incubation at 20°C in 2 thighs characterised by high weight, low number of days of resting and anomalous physiochemical characteristics [one for very low NaCl concentration (1.59%, the other for elevated pH (6.27 and both for high water activity values (>0.970]. The results of this research confirm that the cold resting step is a critical phase in the production process of Parma ham for the investigated hazard. Based on the present study, the long resting phase adopted in the manufacturing of Parma ham is proven effective to prevent the growth of C. botulinum, an event which could not otherwise be excluded if the hams were processed under less

Novel Botulinum Neurotoxins: Exploring Underneath the Iceberg Tip.

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Tehran, Domenico Azarnia; Pirazzini, Marco

2018-05-10

Botulinum neurotoxins (BoNTs), the etiological agents of botulism, are the deadliest toxins known to humans. Yet, thanks to their biological and toxicological features, BoNTs have become sophisticated tools to study neuronal physiology and valuable therapeutics for an increasing number of human disorders. BoNTs are produced by multiple bacteria of the genus Clostridium and, on the basis of their different immunological properties, were classified as seven distinct types of toxin. BoNT classification remained stagnant for the last 50 years until, via bioinformatics and high-throughput sequencing techniques, dozens of BoNT variants, novel serotypes as well as BoNT-like toxins within non-clostridial species have been discovered. Here, we discuss how the now “booming field” of botulinum neurotoxin may shed light on their evolutionary origin and open exciting avenues for future therapeutic applications.

Novel Botulinum Neurotoxins: Exploring Underneath the Iceberg Tip

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Domenico Azarnia Tehran

2018-05-01

Full Text Available Botulinum neurotoxins (BoNTs, the etiological agents of botulism, are the deadliest toxins known to humans. Yet, thanks to their biological and toxicological features, BoNTs have become sophisticated tools to study neuronal physiology and valuable therapeutics for an increasing number of human disorders. BoNTs are produced by multiple bacteria of the genus Clostridium and, on the basis of their different immunological properties, were classified as seven distinct types of toxin. BoNT classification remained stagnant for the last 50 years until, via bioinformatics and high-throughput sequencing techniques, dozens of BoNT variants, novel serotypes as well as BoNT-like toxins within non-clostridial species have been discovered. Here, we discuss how the now “booming field” of botulinum neurotoxin may shed light on their evolutionary origin and open exciting avenues for future therapeutic applications.

Efficacy of Botulinum Toxin Injections in the Treatment of Various Types of Facial Region Disorders

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Arzu Çoban

2012-12-01

Full Text Available OBJECTIVE: Local injection of botulinum toxin is a highly effective treatment option for a wide range of movement disorders and there are reliable sources of information on its indications, effects and safety in clinical practice. In this study, we report our experience with botulinum toxin in the treatment of facial region disorders. METHODS: Patients who had been followed in the Botulinum Toxin Outpatient Clinic of the Neurology Department were retrospectively evaluated. Two preparations of botulinum toxin type A (BT-A were used. The efficacy of BT-A injections was rated according to the improvement in symptoms as follows: marked - 75-100% improvement, good - 50-74%, moderate - 25-49%, and insufficient - less than 25% symptom relief. RESULTS: One hundred eighty-two patients (73 male, 109 female with various facial region disorders were included. The efficacy rates for patients who had very good and good improvement were high in the treatment of blepharospasm, hemifacial spasm, facial synkinesis, and Meige syndrome and moderate for oromandibular dystonia and hypersalivation. Ptosis was the most common side effect. CONCLUSION: According to our results, botulinum toxin was very effective treatment for blepharospasm, Meige syndrome, hemifacial spasm and facial synkinesis, whereas it demonstrated good efficacy in oromandibular dystonia and hypersalivation

Three enzymatically active neurotoxins of Clostridium botulinum strain Af84: BoNT/A2, /F4, and /F5.

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Kalb, Suzanne R; Baudys, Jakub; Smith, Theresa J; Smith, Leonard A; Barr, John R

2014-04-01

Botulinum neurotoxins (BoNTs) are produced by various species of clostridia and are potent neurotoxins which cause the disease botulism, by cleaving proteins needed for successful nerve transmission. There are currently seven confirmed serotypes of BoNTs, labeled A-G, and toxin-producing clostridia typically only produce one serotype of BoNT. There are a few strains (bivalent strains) which are known to produce more than one serotype of BoNT, producing either both BoNT/A and /B, BoNT/A and /F, or BoNT/B and /F, designated as Ab, Ba, Af, or Bf. Recently, it was reported that Clostridium botulinum strain Af84 has three neurotoxin gene clusters: bont/A2, bont/F4, and bont/F5. This was the first report of a clostridial organism containing more than two neurotoxin gene clusters. Using a mass spectrometry based proteomics approach, we report here that all three neurotoxins, BoNT/A2, /F4, and /F5, are produced by C. botulinum Af84. Label free MS(E) quantification of the three toxins indicated that toxin composition is 88% BoNT/A2, 1% BoNT/F4, and 11% BoNT/F5. The enzymatic activity of all three neurotoxins was assessed by examining the enzymatic activity of the neurotoxins upon peptide substrates, which mimic the toxins' natural targets, and monitoring cleavage of the substrates by mass spectrometry. We determined that all three neurotoxins are enzymatically active. This is the first report of three enzymatically active neurotoxins produced in a single strain of Clostridium botulinum.

Botulinum toxin in preparation of oral cavity for microsurgical reconstruction.

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Corradino, Bartolo; Di Lorenzo, Sara; Mossuto, Carmela; Costa, Renato Patrizio; Moschella, Francesco

2010-01-01

Infiltration of botulinum toxin in the major salivary glands allows a temporary reduction of salivation that begins 8 days afterwards and returns to normal within 2 months. The inhibition of salivary secretion, carried out before the oral cavity reconstructive surgery, could allow a reduction of the incidence of oro-cutaneous fistulas and local complications. Saliva stagnation is a risk factor for patients who have to undergo reconstructive microsurgery of the oral cavity, because of fistula formation and local complications in the oral cavity. The authors suggest infiltration of botulinum toxin in the major salivary glands to reduce salivation temporarily during the healing stage. During the preoperative stage, 20 patients with oral cavity carcinoma who were candidates for microsurgical reconstruction underwent sialoscintigraphy and a quantitative measurement of the salivary secretion. Injection of botulinum toxin was carried out in the salivary glands 4 days before surgery. The saliva quantitative measurement was repeated 3 and 8 days after infiltration, sialoscintigraphy after 15 days. In all cases, the saliva quantitative measurement revealed a reduction of 50% and 70% of the salivary secretion after 72 h and 8 days, respectively. A lower rate of local complications was observed.

Use of botulinum A toxin for proctalgia fugax-a case report of successful treatment.

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Grigoriou, Marios; Ioannidis, Aristeidis; Kofina, Konstantinia; Efthimiadis, Christoforos

2017-11-01

Proctalgia fugax is considered as intermittent anal pain of unknown etiology; a variety of treatments have been used, without, however, permanent results. Injection of botulinum A toxin is recently suggested as an alternative option. We present the case of a woman presenting proctalgia fugax that was untreatable through other current forms of treatment. After two administrations of botulinum A toxin, 80 units and 100 units each, the patient remained asymptomatic on 8-month follow-up control. Botulinum A toxin injection can reduce internal anal sphincter pressure, leading to relief of symptoms, and seems a promising option with minimal morbidity in cases on proctalgia fugax that does not respond to other current treatments.

Use of botulinum A toxin for proctalgia fugax—a case report of successful treatment

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Grigoriou, Marios; Ioannidis, Aristeidis; Efthimiadis, Christoforos

2017-01-01

Abstract Proctalgia fugax is considered as intermittent anal pain of unknown etiology; a variety of treatments have been used, without, however, permanent results. Injection of botulinum A toxin is recently suggested as an alternative option. We present the case of a woman presenting proctalgia fugax that was untreatable through other current forms of treatment. After two administrations of botulinum A toxin, 80 units and 100 units each, the patient remained asymptomatic on 8-month follow-up control. Botulinum A toxin injection can reduce internal anal sphincter pressure, leading to relief of symptoms, and seems a promising option with minimal morbidity in cases on proctalgia fugax that does not respond to other current treatments. PMID:29218214

Toxin formation by Clostridium botulinum type B in radurized fish

International Nuclear Information System (INIS)

Suhadi, F.; Thayib, S.S.

1981-01-01

The relation between maximum storage life and earliest toxin formation by proteolytic and nonproteolytic strains of C. botulinum type B in irradiated and unirradiated raw fish was determinated. The fish species used were Rastrelliger sp., Euthynnus sp. and Scomberomorus sp. Uninoculated fish samples held under the same treatment conditions were evaluated for the estimation of storage life by untrained panelist. The results showed that a storage temperature at or lower than 5.6 0 C is recommended in order to avoid botulism hazard caused by nonproteolytic type B. When the samples were inoculated with spores of proteolytic strains, no toxic samples were found during the storage life in all treatments with storage temperatures at or lower than 10.2 0 C. Toxin formation by proteolytic strains of C. botulinum type B in boiled (''Pindang'') chub mackerel (Rastrelliger sp.) under storage at ambient temperatures (27-31 0 C) was also determinated. The results showed that in the samples which were inoculated before the process of ''Pindang'', the earliest toxin formations were detected after the samples were spoiled regardless of the irradiation dose, strain and inoculum level; while in control unsalted samples, toxin was detected before or after the samples were spoiled, depending on the strain and inoculum level. Salt content in ordinary ''Pindang'' fish plays a major role both in extension of the storage life and the delay in toxin formation. When the samples were inoculated after the process of ''Pindang'', toxin was detected before or after the samples were spoiled, depending on the strain, salt content, irradiation dose and inoculum level. Irradiation does not prevent the toxin formation in ''Pindang'' fish if the samples are heavily contaminated with proteolytic strains of C. botulinum type B after cooking. (author)

[Spasm of the near reflex. Treatment with botulinum toxin].

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Merino, P; Rojas, P; Gómez de Liaño, P; Franco Iglesias, G

2015-05-01

A 38-year old female with diplopia and esotropia, with limitation of ocular abduction in both eyes, with full abduction after doll's head rotation also being observed. She was diagnosed with spasm of the near reflex. Treatment with injections of botulinum toxin in both medial rectus has temporally resolved the convergence spasm. Near reflex spasm is characterized as miosis, pseudomyopia, and convergent strabismus that lead to diplopia, blurred vision, headache, and variable, progressive, and intermittent esotropia. As the spasm worsens there will be limited ocular versions and ductions simulating a sixth nerve palsy. Botulinum toxin may be effective in some cases. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Cellular Entry of Clostridium perfringens Iota-Toxin and Clostridium botulinum C2 Toxin

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Masaya Takehara

2017-08-01

Full Text Available Clostridium perfringens iota-toxin and Clostridium botulinum C2 toxin are composed of two non-linked proteins, one being the enzymatic component and the other being the binding/translocation component. These latter components recognize specific receptors and oligomerize in plasma membrane lipid-rafts, mediating the uptake of the enzymatic component into the cytosol. Enzymatic components induce actin cytoskeleton disorganization through the ADP-ribosylation of actin and are responsible for cell rounding and death. This review focuses upon the recent advances in cellular internalization of clostridial binary toxins.

Botulinum toxin for the management of bladder dysfunction.

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Schurch, Brigitte

2006-01-01

This review highlights a recent innovation in the medical treatment of detrusor overactivity (DO). Anticholinergics are usually the gold standard to treat bladder overactivity. Adverse effects and lack of efficacy are the two main causes for considering alternative treatments. Until recently, invasive surgery (mainly bladder augmentation) was the only available treatment option for patients with intractable DO. This article considers botulinum toxin type A (BTX-A) injection as an alternative treatment to surgery in patients with DO who do not respond to anticholinergic therapy. To identify papers for inclusion in this review, we searched PubMed with the keywords 'botulinum toxin', 'overactive bladder', 'urinary incontinence' and 'neurogenic bladder' for the years 2000-5. Review articles were not included. Abstracts were cited only if they contained important new information. Experimental animal studies and articles or book chapters related to the use of botulinum toxin for other indications (such as achalasia and cervical dystonia) were analysed with regard to the mechanisms of action of botulinum toxin. From this review, it appears that BTX-A injection into the detrusor muscle is a very effective method for treating urinary incontinence secondary to neurogenic detrusor overactivity (NDO), as well as urinary incontinence due to idiopathic overactive bladder (IDO). In both conditions, the duration of effect seems to be at least 6 months. Overall success rates seem to be similar in both patient populations. For NDO, only one evidence-based medicine level 1 study is available, whereas for IDO, only evidence-based medicine level 3 or 4 studies have been published. Particularly in this latter indication, injection technique and outcome parameters vary from study to study and need to be standardised. Without randomised controlled studies aimed at comparing different techniques and dosages, it remains difficult to decide what technique is optimal for treating patients

Treatment Efficacy of Electromyography versus Fiberscopy-Guided Botulinum Toxin Injection in Adductor Spasmodic Dysphonia Patients: A Prospective Comparative Study

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Kim, Jae Wook; Park, Jae Hong; Park, Ki Nam; Lee, Seung Won

2014-01-01

Introduction. This study prospectively evaluates and compares the treatment efficacy of botulinum toxin injection under electromyography guidance (EMG group) and percutaneous botulinum toxin injection under flexible fiberscopic guidance (fiberscopy group). Methods. Thirty patients with adductor spasmodic dysphonia (ADSD), who had never received treatment, were randomly allocated into EMG- or fiberscopy-guided botulinum toxin injections between March 2008 and February 2010. We assessed acoustic and aerodynamic voice parameters, and the voice handicap index (VHI) before injection and at 1, 3, and 6 months after injection. Results. The mean total dosage of botulinum toxin was similar for both groups: 1.7 ± 0.5 U for the EMG group and 1.8 ± 0.4 U for the fiberscopy group (P > 0.05). There were no significant differences in outcomes between the two groups in either the duration of effectiveness or complications such as breathy voice and aspiration. Conclusion. Botulinum toxin injection under fiberscopic guidance is a viable alternative to EMG-guided botulinum toxin injection for the treatment of adductor spasmodic dysphonia when EMG equipment is unavailable. PMID:25383369

Treatment Efficacy of Electromyography versus Fiberscopy-Guided Botulinum Toxin Injection in Adductor Spasmodic Dysphonia Patients: A Prospective Comparative Study

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Jae Wook Kim

2014-01-01

Full Text Available Introduction. This study prospectively evaluates and compares the treatment efficacy of botulinum toxin injection under electromyography guidance (EMG group and percutaneous botulinum toxin injection under flexible fiberscopic guidance (fiberscopy group. Methods. Thirty patients with adductor spasmodic dysphonia (ADSD, who had never received treatment, were randomly allocated into EMG- or fiberscopy-guided botulinum toxin injections between March 2008 and February 2010. We assessed acoustic and aerodynamic voice parameters, and the voice handicap index (VHI before injection and at 1, 3, and 6 months after injection. Results. The mean total dosage of botulinum toxin was similar for both groups: 1.7 ± 0.5 U for the EMG group and 1.8 ± 0.4 U for the fiberscopy group (P>0.05. There were no significant differences in outcomes between the two groups in either the duration of effectiveness or complications such as breathy voice and aspiration. Conclusion. Botulinum toxin injection under fiberscopic guidance is a viable alternative to EMG-guided botulinum toxin injection for the treatment of adductor spasmodic dysphonia when EMG equipment is unavailable.

Treatment efficacy of electromyography versus fiberscopy-guided botulinum toxin injection in adductor spasmodic dysphonia patients: a prospective comparative study.

Science.gov (United States)

Kim, Jae Wook; Park, Jae Hong; Park, Ki Nam; Lee, Seung Won

2014-01-01

This study prospectively evaluates and compares the treatment efficacy of botulinum toxin injection under electromyography guidance (EMG group) and percutaneous botulinum toxin injection under flexible fiberscopic guidance (fiberscopy group). Thirty patients with adductor spasmodic dysphonia (ADSD), who had never received treatment, were randomly allocated into EMG- or fiberscopy-guided botulinum toxin injections between March 2008 and February 2010. We assessed acoustic and aerodynamic voice parameters, and the voice handicap index (VHI) before injection and at 1, 3, and 6 months after injection. The mean total dosage of botulinum toxin was similar for both groups: 1.7 ± 0.5 U for the EMG group and 1.8 ± 0.4 U for the fiberscopy group (P > 0.05). There were no significant differences in outcomes between the two groups in either the duration of effectiveness or complications such as breathy voice and aspiration. Botulinum toxin injection under fiberscopic guidance is a viable alternative to EMG-guided botulinum toxin injection for the treatment of adductor spasmodic dysphonia when EMG equipment is unavailable.

Comparative study of biological activity of four botulinum toxin type A preparations in mice.

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Chung, Myung Eun; Song, Dae Heon; Park, Joo Hyun

2013-01-01

Units of available botulinum toxin preparations are not interchangeable, and the dose-conversion ratios between such preparations remain controversial. To compare the efficacy and safety of four botulinum toxin type A preparations. Murine gastrocnemius compound muscle action potentials (CMAPs) were recorded before and after injecting the four botulinum toxin preparations (onabotulinumtoxinA, abobotulinumtoxinA, new botulinum toxin, and incobotulinumtoxinA). In all preparations, CMAP amplitudes decreased until 4 days after receiving the injection and then gradually recovered. On postinjection day 84, the amplitudes returned to baseline in all groups except the high-dose groups. CMAP amplitude in the contralateral limb also decreased up to postinjection days 4 to 7 and then gradually returned to baseline by postinjection day 28. The dose-conversion ratio between onabotulinumtoxinA and abobotulinumtoxinA was determined to be 1:2.6; previous reports of 1:3 were considered too high. A dose-conversion ratio between onabotulinumtoxinA and new botulinum toxin of 1:1 was deemed appropriate. OnabotulinumtoxinA and incobotulinumtoxinA demonstrated a dose-conversion ratio of 1:1.07. The efficacy of incobotulinumtoxinA was slightly lower than that of onabotulinumtoxinA. These dose-conversion ratios are applicable solely from an efficacy standpoint and not for safety. This study was conducted in mice, so it may not translate perfectly to human applications. © 2012 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

Comparative effectiveness of botulinum toxin versus non-surgical treatments for treating lateral epicondylitis: a systematic review and meta-analysis.

Science.gov (United States)

Lin, Yu-Ching; Wu, Wei-Ting; Hsu, Yu-Chun; Han, Der-Sheng; Chang, Ke-Vin

2018-02-01

To explore the effectiveness of botulinum toxin compared with non-surgical treatments in patients with lateral epicondylitis. Data sources including PubMed, Scopus, Embase and Airity Library from the earliest record to February 2017 were searched. Study design, patients' characteristics, dosage/brand of botulinum toxin, injection techniques, and measurements of pain and hand grip strength were retrieved. The standardized mean differences (SMDs) in pain relief and grip strength reduction were calculated at the following time points: 2-4, 8-12, and 16 weeks or more after injection. Six randomized controlled trials (321 participants) comparing botulinum toxin with placebo or corticosteroid injections were included. Compared with placebo, botulinum toxin injection significantly reduced pain at all three time points (SMD, -0.729, 95% confidence interval [CI], -1.286 to -0.171; SMD, -0.446, 95% CI, -0.740 to -0.152; SMD, -0.543, 95% CI, -0.978 to -0.107, respectively). Botulinum toxin was less effective than corticosteroid at 2-4 weeks (SMD, 1.153; 95% CI, 0.568-1.737) and both treatments appeared similar in efficacy after 8 weeks. Different injection sites and dosage/brand did not affect effectiveness. Botulinum toxin decreased grip strength 2-4 weeks after injection, and high equivalent dose could extend its paralytic effects to 8-12 weeks. When treating lateral epicondylitis, botulinum toxin was superior to placebo and could last for 16 weeks. Corticosteroid and botulinum toxin injections were largely equivalent, except the corticosteroid injections were better at pain relief in the early stages and were associated with less weakness in grip in the first 12 weeks.

Treatment of chronic pain associated with nocturnal bruxism with botulinum toxin. A prospective and randomized clinical study

Science.gov (United States)

Al-Wayli, Hessa

2017-01-01

Background To evaluate the role of botulinum toxin type A (BTX-A) in the treatment of pain associated with nocturnal bruxism. Material and Methods Fifty subjects reporting nocturnal bruxism were recruited for a randomized clinical trial. Twenty five bruxers were injected with botulinum toxin in both masseters, and twenty five were treated with traditional methods of treating bruxism. Patients were evaluated at 3rd week, 2nd and 6th month and one year after injection and then used to calculate bruxism events. Bruxism symptoms were investigated using questionnaires. Results Mean pain score due to Bruxism events in the masseter muscle decreased significantly in the botulinum toxin injection group A (P =0.000, highly significant). However, in the conventional treatment group, mean pain score does not show improvement with time (p>0.05). Conclusions Our results suggest that botulinum toxin injection reduced the mean pain score and number of bruxism events, most likely by decreasing the muscle activity of masseter rather than affecting the central nervous system. Key words:Temporomandibular pain, nocturnal bruxism, botulinum toxin. PMID:28149474

Characterisation of botulinum toxins type A and B, by matrix-assisted laser desorption ionisation and electrospray mass spectrometry

NARCIS (Netherlands)

Baar, B.L.M. van; Hulst, A.G.; Jong, A.L. de; Wils, E.R.J.

2002-01-01

A method earlier developed for the mass spectrometric (MS) identification of tetanus toxin (TTx) was applied to botulinum toxins type A and B (BTxA and BTxB). Botulinum toxins are extremely neurotoxic bacterial toxins, likely to be used as biological warfare agent. Biologically active BTxA and BTxB

Botulinum toxin injection for hypercontractile or spastic esophageal motility disorders: may high-resolution manometry help to select cases?

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Marjoux, S; Brochard, C; Roman, S; Gincul, R; Pagenault, M; Ponchon, T; Ropert, A; Mion, F

2015-01-01

Endoscopic injections of botulinum toxin in the cardia or distal esophagus have been advocated to treat achalasia and spastic esophageal motility disorders. We conducted a retrospective study to evaluate whether manometric diagnosis using the Chicago classification in high-resolution manometry (HRM) would be predictive of the clinical response. Charts of patients with spastic and hypertensive motility disorders diagnosed with HRM and treated with botulinum toxin were retrospectively reviewed at two centers. HRM recordings were systematically reanalyzed, and a patient's phone survey was conducted. Forty-five patients treated between 2008 and 2013 were included. Most patients had achalasia type 3 (22 cases). Other diagnoses were jackhammer esophagus (8 cases), distal esophageal spasm (7 cases), esophagogastric junction outflow obstruction (5 cases), nutcracker esophagus (1 case), and 2 unclassified cases. Botulinum toxin injections were performed into the cardia only in 9 cases, into the wall of the distal esophagus in 19 cases, and in both locations (cardia and distal esophagus) in 17 cases. No complication occurred in 31 cases. Chest pain was noticed for less than 7 days in 13 cases. One death related to mediastinitis occurred 3 weeks after botulinum toxin injection. Efficacy was assessed in 42 patients: 71% were significantly improved 2 months after botulinum toxin, and 57% remained satisfied for more than 6 months. No clear difference was observed in terms of response according to manometric diagnosis; however, type 3 achalasia previously dilated and with normal integrated relaxation pressure (4s-integrated relaxation pressure botulinum toxin. Endoscopic injections of botulinum toxin may be effective in some patients with spastic or hypercontractile esophageal motility disorders. The manometric Chicago classification diagnosis does not seem to predict the results. Prospective randomized trials are required to identify patients most likely to benefit from

Botulinum toxin type A as treatment of partially accommodative esotropia.

Science.gov (United States)

Flores-Reyes, E M; Castillo-López, M G; Toledo-Silva, R; Vargas-Ortega, J; Murillo-Correa, C E; Aguilar-Ruiz, A

2016-03-01

To determine the effectiveness of a botulinum toxin type A injection in both medial rectus muscles in patients with partially accommodative esotropia. Residual deviation and stability of strabismus were evaluated at 18 months follow up. A prospective, analytical, quasi-experimental study was conducted on a cohort of 21 patients who underwent total cycloplegic refraction and with a residual deviation of at least 14 DP. A botulinum toxin type A dose of 5 IU was injected into each medial rectus muscle for a residual deviation greater than 18 DP, with a dose of 2.5 IU being used for a deviation between 14 and 18 DP. Multivariate logistic regression analyses were performed to relate residual deviation to variables recorded as potential predictors. A total of 21 patients were included, 33.3% (n=7) males and 66.6% (n=14) females. Mean visual acuity was -.28±.25 logMAR for right eye (range 0 to -1) and -.42±.31 logMAR for left eye (range 0 to -1.3). Mean angle of residual deviation before application of botulinum toxin was 40.95±8.6DP without spectacles correction, and 22.3±7.99 DP with full cycloplegic refraction. Adverse effects were ptosis in 14.2% (n=3), diplopia 23.8% (n=5), and vertical deviation in 33% (n=7). One patient had a poor outcome, therefore required surgical treatment. At one year follow up, 85.71% of patients showed good results with esotropia of 12 DP or less, dropping to 71.43% at 18 months of follow up. Botulinum toxin type A is an effective long-term treatment with a good response in 71.43% of patients. No predictors of good response were demonstrated. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Botulinum toxin for treatment of restrictive strabismus.

Science.gov (United States)

Merino, Pilar S; Vera, Rebeca E; Mariñas, Laura G; Gómez de Liaño, Pilar S; Escribano, Jose V

To study the types of acquired restrictive strabismus treated in a tertiary hospital and the outcome of treatment with botulinum toxin. We performed a 10-year retrospective study of patients with restrictive strabismus aged ≥18 years who were treated with botulinum toxin. Treatment was considered successful if the final vertical deviation was ≤5 PD, horizontal deviation ≤10 PD, with no head turn or diplopia. We included 27 cases (mean age, 61.9 years). Horizontal strabismus was diagnosed in 11.1%, vertical in 51.9%, and mixed in 37%. Strabismus was secondary to cataract surgery in 6 cases, high myopia in 6, orbital fractures in 5, retinal surgery in 5, Graves ophthalmopathy in 4, and repair of conjunctival injury in 1 case. Diplopia was diagnosed in all patients, head turn in 33.3%. The initial deviation was 14 PD (range, 2-40), the mean number of injections per patient was 1.6 (range, 1-3), and the mean dose was 9.5 IU (range, 2.5-22.5). At the end of follow-up, diplopia was recorded in 59.3%, head turn in 18.5%, surgical treatment in 51.9%, and need for prism glasses in 14.8%. Outcome was successful in 37% of patients (4 high myopia, 3 orbital fractures, 2 post-surgical retinal detachment, and 1 post-cataract surgery). Mean follow-up was 3±1.8 years. Vertical deviation was observed in half of the sample. The most frequent deviation was secondary to cataract surgery and high myopia. Treatment with botulinum toxin was successful in one-third of the patients at the end of follow-up. Copyright © 2016 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

Botulinum toxin detection using AlGaN /GaN high electron mobility transistors

Science.gov (United States)

Wang, Yu-Lin; Chu, B. H.; Chen, K. H.; Chang, C. Y.; Lele, T. P.; Tseng, Y.; Pearton, S. J.; Ramage, J.; Hooten, D.; Dabiran, A.; Chow, P. P.; Ren, F.

2008-12-01

Antibody-functionalized, Au-gated AlGaN /GaN high electron mobility transistors (HEMTs) were used to detect botulinum toxin. The antibody was anchored to the gate area through immobilized thioglycolic acid. The AlGaN /GaN HEMT drain-source current showed a rapid response of less than 5s when the target toxin in a buffer was added to the antibody-immobilized surface. We could detect a range of concentrations from 1to10ng/ml. These results clearly demonstrate the promise of field-deployable electronic biological sensors based on AlGaN /GaN HEMTs for botulinum toxin detection.

Botulinum toxin type a for chronic migraine.

Science.gov (United States)

Ashkenazi, Avi

2010-03-01

Chronic migraine (CM) is the leading cause of chronic daily headache, a common and debilitating headache syndrome. The management of CM patients is challenging, with only limited benefit from available oral preventive medications. Botulinum neurotoxin (BoNT) has been used extensively to treat disorders associated with increased muscle tone. More recent scientific data support an analgesic effect of the toxin. The pharmacokinetic and pharmacodynamic profiles of BoNT make it an appealing candidate for migraine prevention. Results from older clinical trials on the efficacy of the toxin in CM were inconclusive. However, recent trials using more stringent inclusion criteria have shown positive results, supporting the use of the toxin in some patients with this disorder. This review summarizes the scientific data on the analgesic properties of BoNT, as well as the clinical data on the efficacy of the toxin in treating CM.

Binding properties of Clostridium botulinum type C progenitor toxin to mucins.

Science.gov (United States)

Nakamura, Toshio; Takada, Noriko; Tonozuka, Takashi; Sakano, Yoshiyuki; Oguma, Keiji; Nishikawa, Atsushi

2007-04-01

It has been reported that Clostridium botulinum type C 16S progenitor toxin (C16S toxin) first binds to the sialic acid on the cell surface of mucin before invading cells [A. Nishikawa, N. Uotsu, H. Arimitsu, J.C. Lee, Y. Miura, Y. Fujinaga, H. Nakada, T. Watanabe, T. Ohyama, Y. Sakano, K. Oguma, The receptor and transporter for internalization of Clostridium botulinum type C progenitor toxin into HT-29 cells, Biochem. Biophys. Res. Commun. 319 (2004) 327-333]. In this study we investigated the binding properties of the C16S toxin to glycoproteins. Although the toxin bound to membrane blotted mucin derived from the bovine submaxillary gland (BSM), which contains a lot of sialyl oligosaccharides, it did not bind to neuraminidase-treated BSM. The binding of the toxin to BSM was inhibited by N-acetylneuraminic acid, N-glycolylneuraminic acid, and sialyl oligosaccharides strongly, but was not inhibited by neutral oligosaccharides. Both sialyl alpha2-3 lactose and sialyl alpha2-6 lactose prevented binding similarly. On the other hand, the toxin also bound well to porcine gastric mucin. In this case, neutral oligosaccharides might play an important role as ligand, since galactose and lactose inhibited binding. These results suggest that the toxin is capable of recognizing a wide variety of oligosaccharide structures.

Safety of Ultrasound-Guided Botulinum Toxin Injections for Sialorrhea as Performed by Pediatric Otolaryngologists.

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Shariat-Madar, Bahbak; Chun, Robert H; Sulman, Cecille G; Conley, Stephen F

2016-05-01

To evaluate incidence of complications and hospital readmission as a result of ultrasound-guided botulinum toxin injections to manage sialorrhea. Case series with chart review. Children's Hospital of Wisconsin. A case series with chart review was performed of all cases of ultrasound-guided injection of botulinum toxin by pediatric otolaryngologists from March 5, 2010, to September 26, 2014,. Primary outcomes included complications such as dysphagia, aspiration pneumonia, and motor paralysis. Secondary outcomes included hospitalization, intubation, and nasogastric tube placement. There were 48 patients, 111 interventions, and 306 intraglandular injections identified. Botulinum toxin type A and type B were utilized in 4 and 107 operative interventions, respectively. Type A was injected into 4 parotid and 4 submandibular glands, utilizing doses of 20 U per parotid and 30 U per submandibular gland. Type B was injected into 98 parotid and 200 submandibular glands, with average dosing of 923 U per parotid and 1170 U per submandibular gland, respectively. There were 2 instances of subjectively worsening of baseline dysphagia that self-resolved. No cases were complicated by aspiration pneumonia or motor paralysis. No patients required hospital readmission, intubation, or nasogastric tube placement. Prior published data indicated 16% complication incidence with ultrasound-guided injection of botulinum toxin. Our study found a low complication rate (0.6%) with ultrasound-guided injections of botulinum toxin to manage sialorrhea, without cases of aspiration pneumonia or motor paralysis. Of 306 intraglandular injections, there were 2 cases of worsening baseline subjective dysphagia that self-resolved. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

Serial Casting as an Adjunct to Botulinum Toxin Type A Treatment in Children With Cerebral Palsy and Spastic Paraparesis With Scissoring of the Lower Extremities.

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Dai, Alper I; Demiryürek, Abdullah T

2017-06-01

The purpose of this study was to examine whether combination therapy of serial casting and botulinum toxin type A injection can further enhance the effects of botulinum toxin type A in children with cerebral palsy with scissoring of both legs. This study was a prospective and randomized trial. The children were divided into 2 groups, one of which received serial casting after botulinum toxin type A (n = 40), and the other which only received botulinum toxin type A (n = 40). Serial casting started 3 weeks after the botulinum toxin type A. Both groups received physiotherapy. Groups were assessed at baseline then compared at 6 and 12 weeks following the intervention. Significant improvements in Gross Motor Function Measure-66 and Caregiver Health Questionnaire were recorded in both groups ( P botulinum toxin type A in the serial casting group ( P botulinum toxin type A only group. These results suggest that serial casting after botulinum toxin type A can enhance the benefits of botulinum toxin type A in children with cerebral palsy.

Optimal Dosing of Botulinum Toxin for Treatment of Chronic Anal Fissure: A Systematic Review and Meta-Analysis.

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Lin, Jin Xin; Krishna, Sanjeev; Su'a, Bruce; Hill, Andrew G

2016-09-01

Chronic anal fissures are associated with significant morbidity and reduced quality of life. Studies have investigated the efficacy of botulinum toxin with variable results; thus, there is currently no consensus on botulinum toxin dose or injection sites. This study aimed to systematically analyze trials studying the efficacy of botulinum toxin for treatment of chronic anal fissure to identify an optimum dosage and injection regimen. A comprehensive review of the literature was conducted according to PRISMA guidelines. PubMed/Medline, Embase, Scopus, and the Cochrane Library were searched from inception to June 2015. All clinical trials that investigated the efficacy of botulinum toxin for chronic anal fissure were selected according to specific criteria. The interventions used were various doses of botulinum toxin. Clinical outcomes, dosage, and injection site data were evaluated with weighted pooled results for each dosage and 95% confidence intervals. There were 1158 patients, with 661 in botulinum toxin treatment arms, from 18 clinical trials included in this review. The outcomes of interest were 3-month healing, incontinence, and recurrence rates. Meta-regression analysis demonstrated a small decrease in healing rate (0.34%; 95% CI, 0-0.68; p = 0.048) with each increase in dosage, a small increase in incontinence rate (1.02 times; 95% CI, 1.0002-1.049; p = 0.048) with each increase in dosage and a small increase in recurrence rate (1.037 times; 95% CI, 1.018-1.057; p = 0.0002) with each increase in dosage. The optimum injection site could not be determined. This study was limited by weaknesses in the underlying evidence, such as variable quality, short follow-up, and a limited range of doses represented. Fissure healing with lower doses of botulinum toxin is as effective as with high doses. Lower doses also reduce the risk of incontinence and recurrence in the long term.

Pneumatic dilation and botulinum toxin: when and why?

Science.gov (United States)

Bozzi, Rosamaria; Di Martino, Vincenzo; Inzirillo, Antonio; D'Avenia, Eugenio; Inzirillo, Maurizio; Cattaneo, Fabio; Cattaneo, Domenico

2013-01-01

Pneumatic dilation and botulinum toxin:when and why? The endoscopic treatment options of achalasia include botulinum toxin (BT) injection and pneumatic dilation (PD) of the lower esophageal sphincter (LES). BT can reduce the LES pressure by blocking the release of acetylcoline from presynaptic cholinergic nerve terminals in the myenteric plexus. Although the procedure is safe and good initial response is reported, there is a wide variability in the duration of the response and the effect tends to decrease over time. BT is usually recommended for elderly patients or patients with comorbid illnesses, who are poor candidates for more invasive procedures. PD aims at tearing the muscle fibers of the LES and is considered the most effective nonsurgical treatment for achalasia. Technical details of the procedure vary in different institutions and in many clinical settings the choice between PD or minimally invasive surgical myotomy depends upon local expertise in the procedures. Further endoscopic treatment options such as submucosal esophageal myotomy or self-expanding metallic stents are being studied.

Botulinum toxin for conditions of the female pelvis.

Science.gov (United States)

El-Khawand, Dominique; Wehbe, Salim; Whitmore, Kristene

2013-07-01

Botulinum toxin has recently been approved by the Food and Drug Administration (FDA) for the treatment of urinary incontinence associated with neurogenic detrusor overactivity. However, it has also been used off-label for a multitude of other conditions in the female pelvis, including urological, gynecological, and colorectal. This article reviews the most recent data regarding its efficacy and safety, and administration techniques for those conditions. A literature review of the most relevant reports published between 1985 and 2012. Urinary incontinence related to neurogenic detrusor overactivity is currently the only approved indication in the female pelvis. Other supported off-label uses include: idiopathic detrusor overactivity, interstitial cystitis/bladder pain syndrome, detrusor sphincter dyssynergia, high-tone pelvic floor dysfunction, anal fissure, anismus, and functional anal pain. Botulinum toxin may effectively and safely be used in many conditions of the female pelvis. More high quality research is needed to better clarify its role in the therapeutic algorithm for those indications.

Effect of a clown's presence at botulinum toxin injections in children: a randomized, prospective study

DEFF Research Database (Denmark)

Hansen, Lars Kjaersgaard; Kibæk, Maria; Martinussen, Torben

2011-01-01

The effect of the presence of a hospital clown during pediatric procedures has rarely been evaluated. In a pediatric ward, botulinum toxin injection is a painful procedure and a stressful experience for the child. We undertook a study of the effect of the presence of a hospital clown on children...... treated with botulinum toxin in an outpatient setting....

Botulinum toxin (BoNT) and back pain.

Science.gov (United States)

Porta, Mauro; Maggioni, G

2004-02-01

Myofascial pain syndrome is defined as subacute or chronic pain with sensory, motor and autonomic symptoms referred from active trigger points with associated painful dysfunctions. Authors present the usefulness of botulinum toxin A or B (BoNT/A or BoNT/B) injected into target muscles since the toxin is capable of controlling not only the muscular spasm but mostly the pain by alternative mechanisms of action, which are discussed. Posology of BoNT, technical aspects and results are presented. BoNT represents an interesting and useful tool for an adequate management of patients with myofascial pain.

Effect of sodium nitrite on toxin production by Clostridium botulinum in bacon.

Science.gov (United States)

Christiansen, L N; Tompkin, R B; Shaparis, A B; Kueper, T V; Johnston, R W; Kautter, D A; Kolari, O J

1974-04-01

Pork bellies were formulated to 0, 30, 60, 120, 170, or 340 mug of nitrite per g of meat and inoculated with Clostridium botulinum via pickle or after processing and slicing. Processed bacon was stored at 7 or 27 C and assayed for nitrite, nitrate, and botulinal toxin at different intervals. Nitrite levels declined during processing and storage. The rate of decrease was more rapid at 27 than at 7 C. Although not added to the system, nitrate was detected in samples during processing and storage at 7 and 27 C. The amount of nitrate found was related to formulated nitrite levels. No toxin was found in samples incubated at 7 C throughout the 84-day test period. At 27 C, via pickle, inoculated samples with low inoculum (210 C. botulinum per g before processing and 52 per g after processing) became toxic if formulated with 120 mug of nitrite per g of meat or less. Toxin was not detected in bacon formulated with 170 or 340 mug of nitrite per g of meat under these same conditions. Toxin was detected at all formulated nitrite levels in bacon inoculated via the pickle with 19,000 C. botulinum per g (4,300 per g after processing) and in samples inoculated after slicing. However, increased levels of formulated nitrite decreased the probability of botulinal toxin formation in bacon inoculated by both methods.

Mass Spectrometric Detection of Botulinum Neurotoxin by Measuring its Activity in Serum and Milk

Science.gov (United States)

Kalb, Suzanne R.; Pirkle, James L.; Barr, John R.

Botulinum neurotoxins (BoNTs) are bacterial protein toxins which are considered likely agents for bioterrorism due to their extreme toxicity and high availability. A new mass spectrometry based assay called Endopep MS detects and defines the toxin serotype in clinical and food matrices via toxin activity upon a peptide substrate which mimics the toxin's natural target. Furthermore, the subtype of the toxin is differentiated by employing mass spectrometry based proteomic techniques on the same sample. The Endopep-MS assay selectively detects active BoNT and defines the serotype faster and with sensitivity greater than the mouse bioassay. One 96-well plate can be analyzed in under 7 h. On higher level or "hot" samples, the subtype can then be differentiated in less than 2 h with no need for DNA.

The role of botulinum toxin in vasospastic disorders of the hand.

Science.gov (United States)

Neumeister, Michael W

2015-02-01

Raynaud phenomenon may be a primary disorder or associated with a variety of other autoimmune processes. Raynaud phenomenon produces digital vasospasm, which can lead to ischemia and ulceration. The treatment of Raynaud phenomenon has been difficult because multiple medical treatments have not provided uniform resolution of symptoms. Many patients have turned to surgery and sympathectomies for the treatment of unrelenting vasospasm. Botulinum toxin has been shown to be an effective alternative to surgery, with a single treatment being capable of resolving pain and healing ulcer. This article reviews the use of botulinum toxin for the treatment of Raynaud phenomenon. Copyright © 2015 Elsevier Inc. All rights reserved.

Towards new uses of botulinum toxin as a novel therapeutic tool.

Science.gov (United States)

Pickett, Andy; Perrow, Karen

2011-01-01

The uses of botulinum toxin in the fields of neurology, ophthalmology, urology, rehabilitation medicine and aesthetic applications have been revolutionary for the treatment of patients. This non-invasive therapeutic has continually been developed since first discovered in the 1970s as a new approach to what were previously surgical treatments. As these applications develop, so also the molecules are developing into tools with new therapeutic properties in specific clinical areas. This review examines how the botulinum toxin molecule is being adapted to new therapeutic uses and also how new areas of use for the existing molecules are being identified. Prospects for future developments are also considered.

Towards New Uses of Botulinum Toxin as a Novel Therapeutic Tool

Directory of Open Access Journals (Sweden)

Karen Perrow

2011-01-01

Full Text Available The uses of botulinum toxin in the fields of neurology, ophthalmology, urology, rehabilitation medicine and aesthetic applications have been revolutionary for the treatment of patients. This non-invasive therapeutic has continually been developed since first discovered in the 1970s as a new approach to what were previously surgical treatments. As these applications develop, so also the molecules are developing into tools with new therapeutic properties in specific clinical areas. This review examines how the botulinum toxin molecule is being adapted to new therapeutic uses and also how new areas of use for the existing molecules are being identified. Prospects for future developments are also considered.

CRYSTAL STRUCTURE OF CLOSTRIDIUM BOTULINUM NEUROTOXIN SEROTYPE B

International Nuclear Information System (INIS)

SWAMINATHAN, S.; ESWARAMOORTHY, S.

2001-01-01

The toxigenic strains of Clostridium botulinum produce seven serologically distinct types of neurotoxins labeled A - G (EC 3.4.24.69), while Clostridium tetani produces tetanus neurotoxin (EC 3.4.24.68). Botulinum and tetanus neurotoxins (BoNTs and TeNT) are produced as single inactive chains of molecular mass of approximately 150 kDa. Most of these neurotoxins are released after being cleaved into two chains, a heavy chain (HI) of 100 kDa and a light chain (L) of 50 kDa held together by an interchain disulfide bond, by tissue proteinases. BoNT/E is released as a single chain but cleaved by host proteinases[1]. Clostvidium botulinum neurotoxins are extremely poisonous proteins with their LD(sub 50) for humans in the range of 0.1 - 1 ng kg(sup -1)[2]. Botulinum neurotoxins are responsible for neuroparalytic syndromes of botulism characterized by serious neurological disorders and flaccid paralysis. BoNTs block the release of acetylcholine at the neuromuscular junction causing flaccid paralysis while TeNT blocks the release of neurotransmitters like glycine and(gamma)-aminobutyric acid (GABA) in the inhibitory interneurons of the spinal cord resulting in spastic paralysis. In spite of different clinical symptoms, their aetiological agents intoxicate neuronal cells in the same way and these toxins have similar structural organization[3

CRYSTAL STRUCTURE OF CLOSTRIDIUM BOTULINUM NEUROTOXIN SEROTYPE B.

Energy Technology Data Exchange (ETDEWEB)

SWAMINATHAN,S.; ESWARAMOORTHY,S.

2001-11-19

The toxigenic strains of Clostridium botulinum produce seven serologically distinct types of neurotoxins labeled A - G (EC 3.4.24.69), while Clostridium tetani produces tetanus neurotoxin (EC 3.4.24.68). Botulinum and tetanus neurotoxins (BoNTs and TeNT) are produced as single inactive chains of molecular mass of approximately 150 kDa. Most of these neurotoxins are released after being cleaved into two chains, a heavy chain (HI) of 100 kDa and a light chain (L) of 50 kDa held together by an interchain disulfide bond, by tissue proteinases. BoNT/E is released as a single chain but cleaved by host proteinases [1]. Clostvidium botulinum neurotoxins are extremely poisonous proteins with their LD{sub 50} for humans in the range of 0.1 - 1 ng kg{sup -1} [2]. Botulinum neurotoxins are responsible for neuroparalytic syndromes of botulism characterized by serious neurological disorders and flaccid paralysis. BoNTs block the release of acetylcholine at the neuromuscular junction causing flaccid paralysis while TeNT blocks the release of neurotransmitters like glycine and {gamma}-aminobutyric acid (GABA) in the inhibitory interneurons of the spinal cord resulting in spastic paralysis. In spite of different clinical symptoms, their aetiological agents intoxicate neuronal cells in the same way and these toxins have similar structural organization [3].

Bruxism secondary to brain injury treated with Botulinum toxin-A: a case report

Science.gov (United States)

El Maaytah, Mohammed; Jerjes, Waseem; Upile, Tahwinder; Swinson, Brian; Hopper, Colin; Ayliffe, Peter

2006-01-01

We report a successful treatment of bruxism in a patient with anoxic brain injury using botulinum toxin-A (BTX-A). On examination the mouth opening was 0 mm, no feeding was possible through the mouth. Botulinum toxin was injected into the masseter and temporalis; great improvement in trismus and bruxism was noted after 3 weeks. One further treatment improved the mouth opening on the following week and the patient was discharged from our care to be reviewed when required. PMID:17123443

Regulation of Botulinum Neurotoxin Synthesis and Toxin Complex Formation by Arginine and Glucose in Clostridium botulinum ATCC 3502.

Science.gov (United States)

Fredrick, Chase M; Lin, Guangyun; Johnson, Eric A

2017-07-01

Botulinum neurotoxin (BoNT), produced by neurotoxigenic clostridia, is the most potent biological toxin known and the causative agent of the paralytic disease botulism. The nutritional, environmental, and genetic regulation of BoNT synthesis, activation, stability, and toxin complex (TC) formation is not well studied. Previous studies indicated that growth and BoNT formation were affected by arginine and glucose in Clostridium botulinum types A and B. In the present study, C. botulinum ATCC 3502 was grown in toxin production medium (TPM) with different levels of arginine and glucose and of three products of arginine metabolism, citrulline, proline, and ornithine. Cultures were analyzed for growth (optical density at 600 nm [OD 600 ]), spore formation, and BoNT and TC formation by Western blotting and immunoprecipitation and for BoNT activity by mouse bioassay. A high level of arginine (20 g/liter) repressed BoNT production approximately 1,000-fold, enhanced growth, slowed lysis, and reduced endospore production by greater than 1,000-fold. Similar effects on toxin production were seen with equivalent levels of citrulline but not ornithine or proline. In TPM lacking glucose, levels of formation of BoNT/A1 and TC were significantly decreased, and extracellular BoNT and TC proteins were partially inactivated after the first day of culture. An understanding of the regulation of C. botulinum growth and BoNT and TC formation should be valuable in defining requirements for BoNT formation in foods and clinical samples, improving the quality of BoNT for pharmaceutical preparations, and elucidating the biological functions of BoNTs for the bacterium. IMPORTANCE Botulinum neurotoxin (BoNT) is a major food safety and bioterrorism concern and is also an important pharmaceutical, and yet the regulation of its synthesis, activation, and stability in culture media, foods, and clinical samples is not well understood. This paper provides insights into the effects of critical

The point-touch technique for botulinum toxin injection in adductor spasmodic dysphonia: quality of life assessment.

Science.gov (United States)

Morzaria, S; Damrose, E J

2011-07-01

Botulinum toxin injection under electromyographic guidance is the 'gold standard' for adductor spasmodic dysphonia treatment. The point-touch technique, an alternative injection method which relies on anatomical landmarks, is cheaper, quicker and more accessible, but has not yet gained widespread acceptance due to concerns about patient satisfaction. To assess swallowing and voice-related quality of life following point-touch botulinum toxin injection in adductor spasmodic dysphonia patients. Stanford University Voice and Swallowing Center. Prospective case series (evidence level four). Consecutive adductor spasmodic dysphonia patients with a stable botulinum toxin dose-response relationship were recruited prospectively. The Eating Assessment Tool and Voice-Related Quality of Life questionnaires were completed pre-treatment and at 10 and 30 per cent completion of the injection cycle, respectively. Thirty-seven patients completed follow up. The mean total botulinum toxin dose was 0.88 units. Pre-treatment Voice-Related Quality of Life questionnaire results reflected the burden of disease. Post-treatment Eating Assessment Tool and Voice-Related Quality of Life questionnaire results were collected at 2.53 and 7.84 weeks, respectively; the former showed an increase in dysphagia, albeit statistically insignificant, while the latter showed significantly improved scores (both domain and total). The point-touch technique is a viable alternative for botulinum toxin injection in the treatment of adductor spasmodic dysphonia.

[Botulism: structure and function of botulinum toxin and its clinical application].

Science.gov (United States)

Oguma, Keiji; Yamamoto, Yumiko; Suzuki, Tomonori; Fatmawati, Ni Nengah Dwi; Fujita, Kumiko

2012-08-01

Clostridium botulinum produces seven immunological distinct poisonous neurotoxins, A to G, with molecular masses of approximately 150kDa. In acidic foods and culture fluid, the neurotoxins associate with non-toxic components, and form large complexes designated progenitor toxins. The progenitor toxins are found in three forms named LL, L, and M. These neurotoxins and progenitor toxins were purified, and whole nucleotide sequences of their structure genes were determined. In this manuscript, the structure and function of these toxins, and the application of these toxins to clinical usage have been described.

Effect of Cultured Celery Juice, Temperature, and Product Composition on the Inhibition of Proteolytic Clostridium botulinum Toxin Production.

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Golden, Max C; Wanless, Brandon J; David, Jairus R D; Kottapalli, Bala; Lineback, D Scott; Talley, Ryan J; Glass, Kathleen A

2017-08-01

Clostridium botulinum may be of concern in prepared refrigerated meals, for which strict cold chain management cannot be guaranteed. This study evaluated the effect of temperature, product composition, and cultured celery juice powder (CCJP) as a source of nitrite on the inhibition of botulinum toxin formation in two experimental (meat- and vegetable-based) prepared meals. Data obtained from the challenge study were compared with a published mathematical model to determine whether the model is fail-safe with regard to the tested meals. Treatments were inoculated with proteolytic C. botulinum, vacuum packaged, cooked at 90°C for 10 min, and assayed for botulinum toxin at appropriate intervals in samples stored at 10, 15, or 20°C for up to 8 weeks. None of the treatments stored at 10°C for 8 weeks supported toxin production by proteolytic C. botulinum. The addition of CCJP delayed toxin production by 1 and 3 weeks in cauliflower potatoes and in Dijon pork, respectively, stored at 15°C. Toxin production was delayed by 1 week at 20°C when CCJP was added to the cauliflower potatoes. This study found that the predictive model was fail-safe but was overly conservative for the experimental meals described. Finally, this study confirms that product composition, the addition of nitrite via CCJP, storage time, and temperature play important roles in the inhibition of toxin formation by proteolytic C. botulinum.

[Treatment of proctalgia fugax with botulinum toxin: results in 5 patients].

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Sánchez Romero, A M; Arroyo Sebastián, A; Pérez Vicente, F A; Serrano Paz, P; Candela Polo, F; Calpena Rico, R

2006-03-01

Proctalgia fugax can be defined as transitory but recurrent anal pain. Although its etiology remains unknown, an internal anal sphincter spasm seems to be the most likely, so that the different treatments focus on reducing the pressure of the internal anal sphincter. This study is aimed at evaluating the effectiveness of botulinum A toxin in the treatment of proctalgia fugax. Prospective clinical trial of patients with proctalgia fugax treated with botulinum A toxin at the Outpatient Clinic attached to the Coloproctogy Unit, University Hospital of Elche, from January 1999 to January 2002. The patients included in the study underwent rectal digital examination, anuscopy, rectoscopy, anal manometry and ultrasonography, barium enema and pelvic CT scan to rule out any organic cause for anal pain. The treatment consisted of 25 IU of botulinum A toxin, with a supplementary dose of 50 IU in those patients with persistence of anal pain episodes within the next two months. The patients were reviewed on the first week, second month, sixth month and first and second year. Anal pain was measured by the patients, using a linear analogue scale from 0 to 10, and continence was assessed at every visit using the Cleveland Continence Grading Scale. Five patients were recluted for the study, with a predominance of females (4 vs. 1). Mean age was 45 years. Length of symptoms prior to the treatment was 13 months (range: 6-18 months). Only one female patient required a second dose of botulinum A toxin to handle the anal pain. All the patients healed and remained free of pain up to finishing the follow-up. There were no local complications. Anal manometry showed an increased MRP (mean resting pressure) in comparison to a control group of patients (114 mmHg vs. 66 mmHg; p proctalgia fugax.

Botulinum toxin injection causes hyper-reflexia and increased muscle stiffness of the triceps surae muscle in the rat

DEFF Research Database (Denmark)

Pingel, Jessica; Wienecke, Jacob; Lorentzen, Jakob

2016-01-01

Botulinum toxin is used to diminish spasticity and reduce the risk of development of contractures. Here, we investigated changes in muscle stiffness caused by reflex activity or elastic muscle properties following botulinum toxin injection in the triceps surae muscle in rats. Forty-four rats...... received injection of botulinum toxin in the left triceps surae muscle. Control measurements were performed on the non-injected contralateral side in all rats. Acute experiments were performed 1, 2, 4 and 8 weeks following injection. The triceps surae muscle was dissected free, the Achilles tendon was cut...... and attached to a muscle puller. The resistance of the muscle to stretches of different amplitudes and velocities was systematically investigated. Reflex mediated torque was normalized to the maximal muscle force (Mmax) evoked by supramaximal stimulation of the tibial nerve. Botulinum toxin injection caused...

Use of botulinum A toxin for proctalgia fugax—a case report of successful treatment

OpenAIRE

Grigoriou, Marios; Ioannidis, Aristeidis; Kofina, Konstantinia; Efthimiadis, Christoforos

2017-01-01

Abstract Proctalgia fugax is considered as intermittent anal pain of unknown etiology; a variety of treatments have been used, without, however, permanent results. Injection of botulinum A toxin is recently suggested as an alternative option. We present the case of a woman presenting proctalgia fugax that was untreatable through other current forms of treatment. After two administrations of botulinum A toxin, 80 units and 100 units each, the patient remained asymptomatic on 8-month follow-up ...

Achalasia in Pregnancy: Botulinum Toxin A Injection of Lower Esophageal Sphincter

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Nicole Hooft

2015-01-01

Full Text Available Background. Achalasia, a rare esophageal motility disorder that may cause malnutrition during pregnancy, can result in fetal and maternal morbidity and mortality. Many medical treatment regimens are contraindicated or not tolerated during pregnancy, and surgery is generally avoided due to potential risks to the fetus. Case Report. Severe, medically refractory achalasia in a 23-year-old pregnant woman that caused malnutrition was successfully managed by administering a botulinum toxin A injection to the lower esophageal sphincter. The injection was performed at approximately 14 weeks’ gestation and the patient reported clinically significant relief from dysphagia. She gained weight and ultimately delivered a healthy baby girl at term, but her symptoms returned a few months postpartum. She underwent a second treatment of botulinum toxin A injection, but it offered only one month of relief. Roughly eight months after delivery, the patient underwent a laparoscopic extended Heller myotomy and Dor fundoplication. The patient resumed a normal diet one week postoperatively, and her baby has had no complications. Conclusion. This is only the second reported case of botulinum toxin A injection being used to treat achalasia in pregnancy. This treatment proved to be a safe temporary alternative without the risks of surgery and anesthesia during pregnancy.

Calf muscle volume estimates: Implications for Botulinum toxin treatment?

DEFF Research Database (Denmark)

Bandholm, Thomas; Sonne-Holm, Stig; Thomsen, Carsten

2007-01-01

An optimal botulinum toxin dose may be related to the volume of the targeted muscle. We investigated the suitability of using ultrasound and anthropometry to estimate gastrocnemius and soleus muscle volume. Gastrocnemius and soleus muscle thickness was measured in 11 cadaveric human legs, using...

Incidental Treatment of a Subclinical Chronic Tension-Type Headache by Cosmetic Use of Botulinum Toxin A: A Case Report

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Iselin Saltvig

2017-11-01

Full Text Available Background: Headache is a common disorder of the nervous system; chronic headache in particular may affect quality of life negatively. The pathophysiology is multifactorial and not completely elucidated. Studies have demonstrated the beneficial effects of botulinum toxin A on chronic migraine headaches, but failed to show the same effect on chronic tension-type headaches. Methods: We present the case of a 32-year-old woman who after receiving cosmetic injections with botulinum toxin A for fine lines of the forehead experienced relief of subclinical tension-type headaches. Conclusions: Although the effect of botulinum toxin A on chronic tension-type headaches is limited, several studies demonstrate its pain-modulating effects, and as such it is worth paying attention to this potential beneficial effect when performing cosmetic injections with botulinum toxin A.

Botulinum toxin injection causes hyper-reflexia and increased muscle stiffness of the triceps surae muscle in the rat.

Science.gov (United States)

Pingel, Jessica; Wienecke, Jacob; Lorentzen, Jakob; Nielsen, Jens Bo

2016-12-01

Botulinum toxin is used with the intention of diminishing spasticity and reducing the risk of development of contractures. Here, we investigated changes in muscle stiffness caused by reflex activity or elastic muscle properties following botulinum toxin injection in the triceps surae muscle in rats. Forty-four rats received injection of botulinum toxin in the left triceps surae muscle. Control measurements were performed on the noninjected contralateral side in all rats. Acute experiments were performed, 1, 2, 4, and 8 wk following injection. The triceps surae muscle was dissected free, and the Achilles tendon was cut and attached to a muscle puller. The resistance of the muscle to stretches of different amplitudes and velocities was systematically investigated. Reflex-mediated torque was normalized to the maximal muscle force evoked by supramaximal stimulation of the tibial nerve. Botulinum toxin injection caused severe atrophy of the triceps surae muscle at all time points. The force generated by stretch reflex activity was also strongly diminished but not to the same extent as the maximal muscle force at 2 and 4 wk, signifying a relative reflex hyperexcitability. Passive muscle stiffness was unaltered at 1 wk but increased at 2, 4, and 8 wk (P botulinum toxin causes a relative increase in reflex stiffness, which is likely caused by compensatory neuroplastic changes. The stiffness of elastic elements in the muscles also increased. The data are not consistent with the ideas that botulinum toxin is an efficient antispastic medication or that it may prevent development of contractures. Copyright © 2016 the American Physiological Society.

Centrifugal microfluidic platform for ultrasensitive detection of Botulinum Toxin

Science.gov (United States)

Botulinum neurotoxin – a global public health threat and category A bioterrorism agent - is the most toxic substance known and one of the most challenging toxins to detect due to its lethality at extremely low concentrations. Hence the live-mouse bioassay because of its superior sensitivity, remains...

[Medical care of patients with spasticity following stroke : Evaluation of the treatment situation in Germany with focus on the use of botulinum toxin].

Science.gov (United States)

Kerkemeyer, L; Lux, G; Walendzik, A; Wasem, J; Neumann, A

2017-08-01

Upper limb spasticity is a common complication following stroke. Cohort studies found 19% of post-stroke patients had upper limb spasticity at 3 months and 38% of patients at 12 months. For focal spasticity, intramuscular injections of botulinum toxin are indicated. In Germany, it is assumed that patients with the described indication are undersupplied with botulinum toxin. The aim of the present study is to evaluate the medical care of patients with upper limb spasticity post-stroke with the focus on the use of botulinum toxin as one treatment option. A standardized questionnaire was developed and a postal survey of a representative national random sample of 800 neurologists to capture the actual medical care situation. The response rate amounted to 37% (n = 292). 59% of the neurologists surveyed had never used botulinum toxin. In total, 87% of neurologists noticed barriers regarding the use of botulinum toxin, where the amount of the doctor's remuneration in 40% and the lack of reimbursement of costs in off-label use in 60% were the most commonly used answers. The achievement of an advanced training in using botulinum toxin was also stated as a general obstacle for resident neurologists. Due to a response rate of 37% for the postal survey a selection bias cannot be excluded. Although botulinum toxin is recommended in the national treatment guidelines, many neurologists do not use botulinum toxin. The reasons can be seen from the barriers described.

Occlusion therapy of unilateral amblyopia with botulinum toxin induced ptosis.

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Halkiadakis, Ioannis; Iliaki, Olga; Kalyvianaki, Maria I; Tsilimbaris, Miltiadis K

2007-01-01

In order to evaluate the role of botulinum toxin induced ptosis as an occlusion method to treat unilateral deep strabismic amblyopia in two uncooperative children, we injected 0.2 ml of diluted botulinum toxin in the levator palpaebrae; low sedation was necessary in one of the two children. In both cases a marked ptosis was achieved, which lasted about four weeks and then gradually resolved completely. The visual acuity of the ablyopic eye increased in both children, making patching easy thereafter. One child developed amblyopia in the injected eye, which was handled successfully using part-time occlusion. No other side effects were noted. Whether this new method could be a simple, safe and effective alternative method of occlusion for the treatment of deep amblyopia in uncooperative children needs to be proven with a larger series of children.

Excellent response rate of anismus to botulinum toxin if rectal prolapse misdiagnosed as anismus ('pseudoanismus') is excluded.

Science.gov (United States)

Hompes, R; Harmston, C; Wijffels, N; Jones, O M; Cunningham, C; Lindsey, I

2012-02-01

Anismus causes obstructed defecation as a result of inappropriate contraction of the puborectalis/external sphincter. Proctographic failure to empty after 30 s is used as a simple surrogate for simultaneous electromyography/proctography. Botulinum toxin is theoretically attractive but efficacy is variable. We aimed to evaluate the efficacy of botulinum toxin to treat obstructed defecation caused by anismus. Botulinum toxin was administered, under local anaesthetic, into the puborectalis/external sphincter of patients with proctographic anismus. Responders (resolution followed by recurrence of obstructed defecation over a 1- to 2-month period) underwent repeat injection. Nonresponders underwent rectal examination under anaesthetic (EUA). EUA-diagnosed rectal prolapse was graded using the Oxford Prolapse Grade 1-5. Fifty-six patients were treated with botulinum toxin. Twenty-two (39%) responded initially and 21/22 (95%) underwent repeat treatment. At a median follow up of 19.2 (range, 7.0-30.4) months, 20/21 (95%) had a sustained response and required no further treatment. Isolated obstructed defecation symptoms (OR = 7.8, P = 0.008), but not proctographic or physiological factors, predicted response on logistic regression analysis. In 33 (97%) of 34 nonresponders, significant abnormalities were demonstrated at EUA: 31 (94%) had a grade 3-5 rectal prolapse, one had internal anal sphincter myopathy and one had a fissure. Exclusion of these alternative diagnoses revised the initial response rate to 96%. Simple proctographic criteria overdiagnose anismus and underdiagnose rectal prolapse. This explains the published variable response to botulinum toxin. Failure to respond should prompt EUA seeking undiagnosed rectal prolapse. A response to an initial dose of botulinum toxin might be considered a more reliable diagnosis of anismus than proctography. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.

Intramural injection with botulinum toxin significantly elongates the pig esophagus

DEFF Research Database (Denmark)

Larsen, Heidi Fhær; Jensen, Thorbjørn Søren Rønn; Rasmussen, Lars

2013-01-01

Surgical treatment of long-gap esophageal atresia (LGEA) is challenging. Methods which facilitate stretching of the esophageal pouches may allow primary anastomosis. Botulinum toxin type A (BTX-A) blocks acetylcholine release in neuromuscular junctions, thereby causing muscle relaxation. We...

A pilot study to evaluate effectiveness of botulinum toxin in treatment of androgenetic alopecia in males

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Sehdev Singh

2017-01-01

Full Text Available Introduction: Androgenetic alopecia is a common form of alopecia with multifactorial etiology. Finasteride and minoxidil are approved by the FDA for the treatment of androgenetic alopecia. Balding scalp is believed to have relative microvascular insufficiency. Blood vessels in the scalp travel through the intramuscular plane. Intramuscular injection of botulinum toxin relaxes muscles and thereby increases blood flow in balding scalp. We conducted a pilot study to evaluate the efficacy of botulinum toxin in androgenetic alopecia management. Material and Methods: The study was conducted in a tertiary care center. A total of 10 male patients with androgenetic alopecia meeting inclusion criteria of the study were included. In the scalp, 30 sites were injected with 5 U of botulinum toxin in each site. Preprocedure photograph taken and evaluation was done, which was repeated after 24 weeks. Efficacy was assessed by photography and self-assessment scoring was done by patients. Results: Of 10 patients, 8 had good to excellent response on photographic assessment. At the end of 24 weeks, 1 patient showed poor and 1 showed fair response to treatment. As per self-assessment, 7of 10 patients showed good to excellent response. Two patients had fair response and 1 patient showed poor response to treatment. Conclusion: Botulinum toxin was found to be safe and effective therapy for the management of androgenetic alopecia in this pilot study. Studies with larger sample size and randomized controlled trials are required to establish the role of botulinum toxin in the management of androgenetic alopecia.

Primary hyperhidrosis: Implications on symptoms, daily life, health and alcohol consumption when treated with botulinum toxin.

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Shayesteh, Alexander; Boman, Jens; Janlert, Urban; Brulin, Christine; Nylander, Elisabet

2016-08-01

Primary hyperhidrosis affects approximately 3% of the population and reduces quality of life in affected persons. Few studies have investigated the symptoms of anxiety, depression and hazardous alcohol consumption among those with hyperhidrosis and the effect of treatment with botulinum toxin. The first aim of this study was to investigate the effect of primary hyperhidrosis on mental and physical health, and alcohol consumption. Our second aim was to study whether and how treatment with botulinum toxin changed these effects. One hundred and fourteen patients answered questionnaires regarding hyperhidrosis and symptoms, including hyperhidrosis disease severity scale (HDSS), visual analog scale (VAS) 10-point scale for hyperhidrosis symptoms, hospital anxiety and depression scale (HADS), alcohol use disorder identification test (AUDIT) and short-form health survey (SF-36) before treatment with botulinum toxin and 2 weeks after. The age of onset of hyperhidrosis was on average 13.4 years and 48% described heredity for hyperhidrosis. Significant improvements were noted in patients with axillary and palmar hyperhidrosis regarding mean HDSS, VAS 10-point scale, HADS, SF-36 and sweat-related health problems 2 weeks after treatment with botulinum toxin. Changes in mean AUDIT for all participants were not significant. Primary hyperhidrosis mainly impairs mental rather than physical aspects of life and also interferes with specific daily activities of the affected individuals. Despite this, our patients did not show signs of anxiety, depression or hazardous alcohol consumption. Treatment with botulinum toxin reduced sweat-related problems and led to significant improvements in HDSS, VAS, HADS and SF-36 in our patients. © 2016 Japanese Dermatological Association.

Assessing adverse effects of intra-articular botulinum toxin A in healthy Beagle dogs: A placebo-controlled, blinded, randomized trial.

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Heikkilä, Helka M; Jokinen, Tarja S; Syrjä, Pernilla; Junnila, Jouni; Hielm-Björkman, Anna; Laitinen-Vapaavuori, Outi

2018-01-01

To investigate the clinical, cytological, and histopathological adverse effects of intra-articularly injected botulinum toxin A in dogs and to study whether the toxin spreads from the joint after the injection. A longitudinal, placebo-controlled, randomized clinical trial was conducted with six healthy laboratory Beagle dogs. Stifle joints were randomized to receive either 30 IU of onabotulinum toxin A or placebo in a 1:1 ratio. Adverse effects and spread of the toxin were examined by evaluating dynamic and static weight-bearing of the injected limbs, by assessing painless range of motion and pain on palpation of joints, and by performing synovial fluid analysis, neurological examination, and electrophysiological recordings at different examination time-points in a 12-week period after the injections. The dogs were then euthanized and autopsy and histopathological examination of joint structures and adjacent muscles and nerves were performed. Intra-articular botulinum toxin A did not cause local weakness or injection site pain. Instead, static weight-bearing and painless range of motion of stifle joints decreased in the placebo limbs. No clinically significant abnormalities associated with intra-articular botulinum toxin A were detected in the neurological examinations. Electrophysiological recordings showed low compound muscle action potentials in two dogs in the botulinum toxin A-injected limb. No significant changes were detected in the synovial fluid. Autopsy and histopathological examination of the joint and adjacent muscles and nerves did not reveal histopathological adverse effects of the toxin. Intra-articular botulinum toxin A does not produce significant clinical, cytological, or histopathological adverse effects in healthy dogs. Based on the electrophysiological recordings, the toxin may spread from the joint, but its clinical impact seems to be low.

Botulinum toxin A for treatment of neurogenic detrusor overactivity and incontinence in patients with spinal cord lesions

DEFF Research Database (Denmark)

Bagi, Per; Biering-Sørensen, Fin

2004-01-01

To evaluate the efficacy of intravesical botulinum toxin A (BTA) in the treatment of severe neurogenic detrusor overactivity (NDO) with incontinence in patients with spinal cord lesions (SCLs).......To evaluate the efficacy of intravesical botulinum toxin A (BTA) in the treatment of severe neurogenic detrusor overactivity (NDO) with incontinence in patients with spinal cord lesions (SCLs)....

Botulinum toxin injection in laryngeal dyspnea.

Science.gov (United States)

Woisard, Virginie; Liu, Xuelai; Bes, Marie Christine Arné; Simonetta-Moreau, Marion

2017-02-01

Data, regarding the use of botulinum toxin (BT-A) in laryngeal dyspnea, are scarce, coming from some cases reports in the literature, including Vocal fold paralysis, laryngeal dystonia, vocal cord dysfunction also called paradoxical motion of the vocal fold (PMVF), and post-neuroleptic laryngeal dyskinesia. There is no consensus regarding the muscles and the doses to inject. The aim of this study is to present a retrospective review of patients treated in our ENT Department by BT-A injection in this indication. This study is a retrospective study describing patients who underwent an injection of botulinum toxin for laryngeal dyspnea in the ENT Department from 2005 to 2015 years. The inclusion criteria were a dyspnea associated with a laryngeal dysfunction, confirmed by flexible fiberoptic nasopharyngolaryngoscopy. Information concerning the causes of the dyspnea, the botulinum toxin BT-A injections procedure, post-injection follow-up, and respiratory outcome were collected for all patients included. In the group of 13 patients included, the main cause identified as principal factor linked with the short breath was: a bilateral VF paralysis (Patel et al., Otolaryngol Head Neck Surg 130:686-689, 7), laryngeal dystonia (Balkissoon and Kenn, Semin Respir Crit Care Med 33:595-605, 2), Anxiety syndrome associated with unilateral vocal fold paralysis or asthma (Marcinow et al., Laryngoscope 124:1425-1430, 3), and an isolated asthma (Zwirner et al., Eur Arch Otorhinolaryngol 254:242-245, 1). Nine out of the thirteen patients were improved by the injections. A BT-A-induced stable benefit for four patients led them to stop the injections in the follow-up. Good outcome was observed in five other patients (main cause: bilateral VP paralysis), allowing a progressive lengthening of the delay between BT-A injections. Four patients did not report a positive risk/benefit ratio after BT-A injections; two of them (with bilateral VF paralysis), because of respiratory side effects and

Longitudinal Phonatory Characteristics after Botulinum Toxin Type A Injection.

Science.gov (United States)

Fisher, Kimberly V.; And Others

1996-01-01

A study investigated the long-term effects of a Botulinum Toxin Type A injection on the glottal competency of a man with adductor spasmodic dysphonia. Results suggest that change in degree of glottal adduction over time can be observed even when vocal instability is present within each recording session. (CR)

Survey of Botulinum Toxin Injections in Anticoagulated Patients: Korean Physiatrists' Preference in Controlling Anticoagulation Profile Prior to Intramuscular Injection.

Science.gov (United States)

Jang, Yongjun; Park, Geun-Young; Park, Jihye; Choi, Asayeon; Kim, Soo Yeon; Boulias, Chris; Phadke, Chetan P; Ismail, Farooq; Im, Sun

2016-04-01

To evaluate Korean physiatrists' practice of performing intramuscular botulinum toxin injection in anticoagulated patients and to assess their preference in controlling the bleeding risk before injection. As part of an international collaboration survey study, a questionnaire survey was administered to 100 Korean physiatrists. Physiatrists were asked about their level of experience with botulinum toxin injection, the safe international normalized ratio range in anticoagulated patients undergoing injection, their tendency for injecting into deep muscles, and their experience of bleeding complications. International normalized ratio injection by 41% of the respondents. Thirty-six respondents replied that the international normalized ratio should be lowered to sub-therapeutic levels before injection, and 18% of the respondents reported that anticoagulants should be intentionally withheld and discontinued prior to injection. In addition, 20%-30% of the respondents answered that they were uncertain whether they should perform the injection regardless of the international normalized ratio values. About 69% of the respondents replied that they did have any standardized protocols for performing botulinum toxin injection in patients using anticoagulants. Only 1 physiatrist replied that he had encountered a case of compartment syndrome. In accordance with the lack of consensus in performing intramuscular botulinum toxin injection in anticoagulated patients, our survey shows a wide range of practices among many Korean physiatrists; they tend to avoid botulinum toxin injection in anticoagulated patients and are uncertain about how to approach these patients. The results of this study emphasize the need for formulating a proper international consensus on botulinum toxin injection management in anticoagulated patients.

[Botulinum toxin: An important complement for facial rejuvenation surgery].

Science.gov (United States)

Le Louarn, C

2017-10-01

The improved understanding of the functional anatomy of the face and of the action of the botulinum toxin A leads us to determine a new injection procedure which consequently decreases the risk of eyebrow and eyelid ptosis and increases the toxin's injection possibilities and efficiencies. With less units of toxin, the technique herein described proposes to be more efficient on more muscles: variable toxin injections concentration adapted to each injected muscle are used. Thanks to a new procedure in the upper face, toxin A injection can be quite close to an endoscopic surgical action. In addition, interesting results are achievable to rejuvenate the lateral canthus with injection on the upper lateral tarsus, to rejuvenate the nose with injection at the alar base, the jawline and the neck region. Lastly, a smoothing effect on the skin (meso botox) is obtained by the anticholinergic action of the toxin A on the dermal receptors. Copyright © 2017. Published by Elsevier Masson SAS.

Muscle disuse caused by botulinum toxin injection leads to increased central gain of the stretch reflex in the rat

DEFF Research Database (Denmark)

Pingel, Jessica; Hultborn, Hans; Naslund-Koch, Lui

2017-01-01

Botulinum toxin (Btx) is used in children with cerebral palsy and other neurological patients to diminish spasticity and reduce the risk of development of contractures. Here, we investigated changes in the central gain of the stretch reflex circuitry in response to botulinum toxin injection...

Botulinum Toxin Therapy: Is Syringe Type Related to Cost-Effectiveness?

Science.gov (United States)

Foglietti, Mark Anthony; Wright, Lauren; Foglietti-Fostyk, Alanna

2018-03-01

Clostridium botulinum toxin is effective through cleaving presynaptic proteins at the neuromuscular junction, which prevents the release of acetylcholine and inhibits muscle contraction. Several serotypes of botulinum toxin (BT) exist; however, only 2 types have been approved by the US Food and Drug Administration for commercial and medical use, A and B. Both types of BT must be administered intramuscularly with a syringe, but the type of syringe is the injector's preference. Which syringe type is most efficient in minimizing product waste and most cost-effective for the patient and provider? We performed a single-center, open-label, analytical study using BT therapy and 2 types of syringes for analytics of cost-effectiveness. OnabotulinumtoxinA was the neuromodulator used in this report. Vials (100 U) of BT A were each reconstituted with 2.5 mL of 0.9% sodium chloride, for a final concentration of 4 U/0.1 mL. High-dead-space syringes are compared with low-dead-space syringes: 1-mL tuberculin (TB) luer slip syringe with detachable 25-gauge needle and 1-mL ultrafine insulin syringe with an attached 31-gauge needle, respectively. After each syringe was evacuated, the TB syringe was noted to contain 0.05 mL of the remaining product in the hub. Providers are discarding approximately 2 U of BT per TB syringe product injection. If the physician uses 30 syringes per day, 3 days a week, for 1 year, it equals to a lost revenue of approximately $155,500 per year. To individualize the cost-effective analysis, average quantity of syringes used per patient and overall patient volume must be considered, with corresponding adjustment of cost and units discarded. The American Society of Plastic Surgeons reported that the use of neuromodulators has increased by approximately 797% from 2000 to 2016. During that period, the price of neuromodulators has also increased by approximately 85%. Considering these statistics, the type of syringe used for BT neuromodular injection is a

The therapeutic use of botulinum toxin in cervical and maxillofacial conditions: an evidence-based review.

Science.gov (United States)

Ihde, Stefan K A; Konstantinovic, Vitomir S

2007-08-01

The role of botulinum toxin as a therapeutic agent for several conditions is expanding. We sought to determine if botulinum toxin is safe and effective in treating patients with cervical dystonia and maxillofacial conditions. Our purpose was to establish a safety and efficacy profile to determine whether or not this treatment may be used prophylactically in patients undergoing dental implant therapy. We performed a systematic search of the literature to identify randomized clinical trials evaluating patients treated with botulinum toxin as an adjunct to dental implant therapy, maxillofacial conditions including temporomandibular disorders (TMD), and cervical dystonia. Four randomized controlled trials (RCTs) met our search criteria in the area of cervical dystonia and chronic facial pain. No RCTs were identified evaluating dental implant therapy. Patients with cervical dystonia exhibited significant improvements in baseline functional, pain, and global assessments compared to placebo. Adverse events were mild and transient with numbers needed to harm (NNH) ranging from 12 to 17. Patients with chronic facial pain improved significantly from baseline in terms of pain compared to placebo. Rates of adverse events were less than 1%. Botulinum toxin appears relatively safe and effective in treating cervical dystonia and chronic facial pain associated with masticatory hyperactivity. No literature exists evaluating its use in dental implantology. Randomized clinical trials are warranted to determine its safety and efficacy in dental implantology and other maxillofacial conditions such as bruxism.

Botulinum toxin in the treatment of orofacial tardive dyskinesia : A single blind study

NARCIS (Netherlands)

Slotema, Christina W.; van Harten, Peter N.; Bruggeman, Richard; Hoek, Hans W.

2008-01-01

Objective: Orofacial tardive dyskinesia (OTD) is difficult to treat and Botulinium Toxin A (BTA) may be an option. Methods: In a single blind (raters were blind) study (N= 12, duration 33 weeks) OTD was treated with Botulinum Toxin A in three consecutive sessions with increasing dosages. The

Value of botulinum toxin injections preceding a comprehensive rehabilitation period for children with spastic cerebral palsy: A cost-effectiveness study.

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Schasfoort, Fabienne; Dallmeijer, Annet; Pangalila, Robert; Catsman, Coriene; Stam, Henk; Becher, Jules; Steyerberg, Ewout; Polinder, Suzanne; Bussmann, Johannes

2018-01-10

Despite the widespread use of botulinum toxin in ambulatory children with spastic cerebral palsy, its value prior to intensive physiotherapy with adjunctive casting/orthoses remains unclear. A pragmatically designed, multi-centre trial, comparing the effectiveness of botulinum toxin + intensive physiotherapy with intensive physiotherapy alone, including economic evaluation. Children with spastic cerebral palsy, age range 4-12 years, cerebral palsy-severity Gross Motor Function Classification System levels I-III, received either botulinum toxin type A + intensive physiotherapy or intensive physiotherapy alone and, if necessary, ankle-foot orthoses and/or casting. Primary outcomes were gross motor func-tion, physical activity levels, and health-related quality-of-life, assessed at baseline, 12 (primary end-point) and 24 weeks (follow-up). Economic outcomes included healthcare and patient costs. Intention-to-treat analyses were performed with linear mixed models. There were 65 participants (37 males), with a mean age of 7.3 years (standard deviation 2.3 years), equally distributed across Gross Motor Function Classification System levels. Forty-one children received botulinum toxin type A plus intensive physio-therapy and 24 received intensive physiotherapy treatment only. At primary end-point, one statistically significant difference was found in favour of intensive physiotherapy alone: objectively measured percentage of sedentary behaviour (-3.42, 95% confidence interval 0.20-6.64, p=0.038). Treatment costs were significantly higher for botulinum toxin type A plus intensive physiotherapy (8,963 vs 6,182 euro, p=0.001). No statistically significant differences were found between groups at follow-up. The addition of botulinum toxin type A to intensive physiotherapy did not improve the effectiveness of rehabilitation for ambulatory children with spastic cerebral palsy and was also not cost-effective. Thus botulinum toxin is not recommended for use in improving gross

Evaluation of the protective effect of Botulinum toxin type A injection on otitis media with effusion.

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Çalım, Ömer Faruk; Yıldırım, Yavuz Selim; Doğan, Remzi; Tuğrul, Selhattin; Gedik, Özge; Özturan, Orhan

2017-09-01

This study makes an analysis of the effect of Botulinum toxin type A on otitis media with effusion in rats. As part of the study, 24 male Wistar Albino rats were divided into three groups: Group 1: Botulinum toxin Type A and Histamıne (intratympanic 0.2 ml = 20 unit BTA); Group 2: Saline and Histamine (intratympanic 0.2 ml 0.9%); Group 3: Histamine (intratympanic 0.2 ml). Histamine (intratympanic 0.2 ml) was administered into the right ear for all groups. DPOAE and ABR tests were carried out on days 5, 10, 15 and 20 from the beginning of the study. There was no significant difference between DPOAE and ABR scores of the groups. In each group, the DPOAE scores for the right ear significantly decreased on day 5 when compared to the basal scores. In each group, there was no significant difference between days 5, 10 and 15 for the right ear. Botulinum toxin type A blocked the secretion of glands in the middle ear and showed no effect to prevent the formation of serous otitis. In addition, it was found out that Botulinum toxin did not lead to any morphological change in the cochlea.

Molecular Evolutionary Constraints that Determine the Avirulence State of Clostridium botulinum C2 Toxin.

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Prisilla, A; Prathiviraj, R; Chellapandi, P

2017-04-01

Clostridium botulinum (group-III) is an anaerobic bacterium producing C2 toxin along with botulinum neurotoxins. C2 toxin is belonged to binary toxin A family in bacterial ADP-ribosylation superfamily. A structural and functional diversity of binary toxin A family was inferred from different evolutionary constraints to determine the avirulence state of C2 toxin. Evolutionary genetic analyses revealed evidence of C2 toxin cluster evolution through horizontal gene transfer from the phage or plasmid origins, site-specific insertion by gene divergence, and homologous recombination event. It has also described that residue in conserved NAD-binding core, family-specific domain structure, and functional motifs found to predetermine its virulence state. Any mutational changes in these residues destabilized its structure-function relationship. Avirulent mutants of C2 toxin were screened and selected from a crucial site required for catalytic function of C2I and pore-forming function of C2II. We found coevolved amino acid pairs contributing an essential role in stabilization of its local structural environment. Avirulent toxins selected in this study were evaluated by detecting evolutionary constraints in stability of protein backbone structure, folding and conformational dynamic space, and antigenic peptides. We found 4 avirulent mutants of C2I and 5 mutants of C2II showing more stability in their local structural environment and backbone structure with rapid fold rate, and low conformational flexibility at mutated sites. Since, evolutionary constraints-free mutants with lack of catalytic and pore-forming function suggested as potential immunogenic candidates for treating C. botulinum infected poultry and veterinary animals. Single amino acid substitution in C2 toxin thus provides a major importance to understand its structure-function link, not only of a molecule but also of the pathogenesis.

Structure-function discrepancy in Clostridium botulinum C3 toxin for its rational prioritization as a subunit vaccine.

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Prathiviraj, R; Prisilla, A; Chellapandi, P

2016-06-01

Clostridium botulinum is anaerobic pathogenic bacterium causing food-born botulism in human and animals by producing botulinum neurotoxins A-H, C2, and C3 cytotoxins. Physiological group III strains (type C and D) of this bacterium are capable of producing C2 and C3 toxins in cattle and avian. Herein, we have revealed the structure-function disparity of C3 toxins from two different C. botulinum type C phage (CboC) and type D phage (CboD) to design avirulent toxins rationally. Structure-function discrepancy of the both toxins was computationally evaluated from their homology models based on the conservation in sequence-structure-function relationships upon covariation and point mutations. It has shown that 8 avirulent mutants were generated from CboC of 34 mutants while 27 avirulent mutants resulted from CboD mutants. No major changes were found in tertiary structure of these toxins; however, some structural variations appeared in the coiled and loop regions. Correlated mutation on the first residue would disorder or revolutionize the hydrogen bonding pattern of the coevolved pairs. It suggested that the residues coupling in the local structural environments were compensated with coevolved pairs so as to preserve a pseudocatalytic function in the avirulent mutants. Avirulent mutants of C3 toxins have shown a stable structure with a common blue print of folding process and also attained a near-native backrub ensemble. Thus, we concluded that selecting the site-directed mutagenesis sites are very important criteria for designing avirulent toxins, in development of rational subunit vaccines, to cattle and avian, but the vaccine specificity can be determined by the C3 toxins of C. botulinum harboring phages.

Structural constraints-based evaluation of immunogenic avirulent toxins from Clostridium botulinum C2 and C3 toxins as subunit vaccines.

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Prisilla, A; Prathiviraj, R; Sasikala, R; Chellapandi, P

2016-10-01

Clostridium botulinum (group-III) is an anaerobic bacterium producing C2 and C3 toxins in addition to botulinum neurotoxins in avian and mammalian cells. C2 and C3 toxins are members of bacterial ADP-ribosyltransferase superfamily, which modify the eukaryotic cell surface proteins by ADP-ribosylation reaction. Herein, the mutant proteins with lack of catalytic and pore forming function derived from C2 (C2I and C2II) and C3 toxins were computationally evaluated to understand their structure-function integrity. We have chosen many structural constraints including local structural environment, folding process, backbone conformation, conformational dynamic sub-space, NAD-binding specificity and antigenic determinants for screening of suitable avirulent toxins. A total of 20 avirulent mutants were identified out of 23 mutants, which were experimentally produced by site-directed mutagenesis. No changes in secondary structural elements in particular to α-helices and β-sheets and also in fold rate of all-β classes. Structural stability was maintained by reordered hydrophobic and hydrogen bonding patterns. Molecular dynamic studies suggested that coupled mutations may restrain the binding affinity to NAD(+) or protein substrate upon structural destabilization. Avirulent toxins of this study have stable energetic backbone conformation with a common blue print of folding process. Molecular docking studies revealed that avirulent mutants formed more favorable hydrogen bonding with the side-chain of amino acids near to conserved NAD-binding core, despite of restraining NAD-binding specificity. Thus, structural constraints in the avirulent toxins would determine their immunogenic nature for the prioritization of protein-based subunit vaccine/immunogens to avian and veterinary animals infected with C. botulinum. Copyright © 2016 Elsevier B.V. All rights reserved.

Channels Formed by Botulinum, Tetanus, and Diphtheria Toxins in Planar Lipid Bilayers: Relevance to Translocation of Proteins across Membranes

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Hoch, David H.; Romero-Mira, Miryam; Ehrlich, Barbara E.; Finkelstein, Alan; Dasgupta, Bibhuti R.; Simpson, Lance L.

1985-03-01

The heavy chains of both botulinum neurotoxin type B and tetanus toxin form channels in planar bilayer membranes. These channels have pH-dependent and voltage-dependent properties that are remarkably similar to those previously described for diphtheria toxin. Selectivity experiments with anions and cations show that the channels formed by the heavy chains of all three toxins are large; thus, these channels could serve as ``tunnel proteins'' for translocation of active peptide fragments. These findings support the hypothesis that the active fragments of botulinum neurotoxin and tetanus toxin, like that of diphtheria toxin, are translocated across the membranes of acidic vesicles.

Experience with botulinum toxin in the treatment of cerebral palsy

African Journals Online (AJOL)

Institute of Child Health, Red Cross War Memorial Children's. Hospital and University of .... A majority of the children in this study showed definite short- term benefit following botulinum toxin injection and this form of therapy constitutes ... repeated when necessary as long as the spasticity remains dynamic. Patients with ...

Diagnosis and management with botulinum toxin in 11 cases of laryngeal synkinesis.

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Lekue, Asier; García-López, Isabel; Santiago, Susana; Del Palacio, Antonio; Gavilán, Javier

2015-09-01

Laryngeal synkinesis is a vocal fold movement disorder produced by a misdirected reinnervation after a recurrent laryngeal nerve injury. Its symptoms differ greatly between patients, requiring diverse therapeutical approaches. We aim to describe our experience in the diagnosis and treatment of different laryngeal synkinesis presentations. 11 patients diagnosed between 2011 and 2014 in a tertiary referral center with laryngeal synkinesis confirmed by laryngeal electromyography were included in our study. All medical records and laryngoscopic and electromyographic data were reviewed retrospectively. Four patients had previous unilateral vocal fold palsy and seven had a bilateral palsy with different degrees of clinical involvement. All of them showed paradoxical movements during inhalation in videofibrolaryngoscopic examination. Laryngeal electromyography confirmed the diagnosis of laryngeal synkinesis. Dyspnea was the main presentation symptom. Three patients with mild symptoms were not treated. Patients with unilateral vocal fold immobility were successfully treated with periodic botulinum toxin injections. Patients with bilateral immobility had a good initial response to botulinum toxin, although in some of them, a posterior cordectomy had to be finally performed. In conclusion, laryngeal synkinesis is a heterogeneous clinic entity that appears in patients with unilateral or bilateral vocal fold paralysis. Videofibrolaryngoscopy and laryngeal electromyography are essential to a correct diagnosis. Botulinum toxin injections are the main treatment for symptomatic cases, even if in bilateral palsy cases more aggressive treatments are often required.

Botulinum neurotoxin formulations: overcoming the confusion

Directory of Open Access Journals (Sweden)

Samizadeh S

2018-05-01

Full Text Available Souphiyeh Samizadeh,1 Koenraad De Boulle2 1Great British Academy of Aesthetic Medicine, London, UK; 2Aalst Dermatology Clinic, Aalst, Belgium Abstract: Botulinum toxin A is produced by anaerobic spore-forming bacteria and is used for various therapeutic and cosmetic purposes. Botulinum toxin A injections are the most popular nonsurgical procedure worldwide. Despite an increased demand for botulinum toxin A injections, the clinical pharmacology and differences in formulation of commonly available products are poorly understood. The various products available in the market are unique and vary in terms of units, chemical properties, biological activities, and weight, and are therefore not interchangeable. For safe clinical practice and to achieve optimal results, the practitioners need to understand the clinical issues of potency, conversion ratio, and safety issues (toxin spread and immunogenicity. In this paper, the basic clinical pharmacology of botulinum toxin A and differences between onabotulinum toxin A, abobotulinum toxin A, and incobotulinum toxin A are discussed. Keywords: botulinum toxin, botulinum neurotoxin, moiety, protein complexes

The botulinum toxin legend of Reinhard Heydrich's death: The end of "Himmler's brain".

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Tatu, Laurent; Jost, Wolfgang; Bogousslavsky, Julien

2017-07-04

The high-ranking German Nazi Reinhard Heydrich (1904-1942) was one of the main organizers of the mass murder of Jews during the Second World War. He died on June 4, 1942, in Prague after having been wounded in Operation Anthropoid planned by the British intelligence services. Since the 1970s and 1980s, Heydrich's death has been frequently presented in British, American, and French literature as the consequence of a bacteriologic attack. Botulinum toxin would have been used in the grenades or ammunition. We discuss the botulinum toxin hypothesis using the now declassified British archives of Operation Anthropoid and of the chemical and bacteriologic warfare centers to assess this hypothesis. © 2017 American Academy of Neurology.

Botulinum toxin efficacy in the treatment of patients with spasmodic dysphonia

Directory of Open Access Journals (Sweden)

Svetel Marina

2007-01-01

Full Text Available Background/Aim. Spasmodic dysphonia (DS is a disabling speech disturbance appearing as the consequence of dystonic vocal folds contraction. Its intermittent appearance in the laryngeal muscles causes vocal function discontinuation. The quality of life of these patients is significantly disturbed. Surgical and a medical therapy appear to be inadequate and unsuccessful ones of no steady improvement. It is the botulinum toxin therapy that proved to be highly efficacious one, with the established improvement in 80−100% of patients. The aim of our study was to evaluate the efficacy of botulinum toxin therapy in patients with SD and to show our preliminary results. Methods. The study included 10 patients with adductor spasmodic dysphonia. After diagnostic procedures, botulinum toxin was applied either in one or both vocal folds, in doses of 12−16 units each. In our study we applied indirect technique originally developed by Hočevar and Pirtošek. Perceptive voice and speech analysis was performed prior to and after the instillation of botuline toxin as per structured Scale of pathological characteristics of voice and speech appearing in the spasmodic dysphonia. Results. The majority of our patients experienced both subjective improvement and the improvement in the terms of the quality of life, Voice Henolicap Index − (VHI that was rated as rather significant one (t = 3.562; p = 0.006. Conclusion. Regardless unquestionable improvement of definite phonation, further function restitution requires individual vocal therapy and psychotherapy. Vocal therapy includes structural vocal techniques which reduce degree of vocal tension and rapid changes in the power and the height of voice. Further investigations are necessary for the scope of the definition of a standardized therapeutically procedure for spasmodic dysphonia treatment which comprises multidisciplinary approach in diagnosis, therapy and treatment efficacy evaluation.

Immuno-detection of cleaved SNAP-25 from differentiated mouse embryonic stem cells provides a sensitive assay for determination of botulinum A toxin and antitoxin potency.

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Yadirgi, G; Stickings, P; Rajagopal, S; Liu, Y; Sesardic, D

2017-12-01

Botulinum toxin type A is a causative agent of human botulism. Due to high toxicity and ease of production it is classified by the Centres for Disease Control and Prevention as a category A bioterrorism agent. The same serotype, BoNT/A, is also the most widely used in pharmaceutical preparations for treatment of a diverse range of neuromuscular disorders. Traditionally, animals are used to confirm the presence and activity of toxin and to establish neutralizing capabilities of countermeasures in toxin neutralization tests. Cell based assays for BoNT/A have been reported as the most viable alternative to animal models, since they are capable of reflecting all key steps (binding, translocation, internalization and cleavage of intracellular substrate) involved in toxin activity. In this paper we report preliminary development of a simple immunochemical method for specifically detecting BoNT/A cleaved intracellular substrate, SNAP-25, in cell lysates of neurons derived from mouse embryonic stem cells. The assay offers sensitivity of better than 0.1LD50/ml (3fM) which is not matched by other functional assays, including the mouse bioassay, and provides serotype specificity for quantitative detection of BoNT/A and anti-BoNT/A antitoxin. Subject to formal validation, the method described here could potentially be used as a substitute for the mouse bioassay to measure potency and consistency of therapeutic products. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Treatment of hemifacial spasm with botulinum A toxin. Results and rationale.

Science.gov (United States)

Gonnering, R S

1986-01-01

Hemifacial spasm is characterized by unilateral, periodic, tonic contractions of facial muscles, thought to be caused by mechanical compression at the root-exit zone of the facial nerve. Electrophysiologic abnormalities such as ectopic excitation and synkinesis are typical. Although posterior fossa microsurgical nerve decompression is successful in bringing about relief of the spasm in most cases, it carries a risk to hearing. As an alternative treatment, 15 patients with hemifacial spasm were given a total of 41 sets of injections with botulinum A toxin, with a mean follow-up of 14.3 +/- 1.1 months. Relief of symptoms lasted a mean of 108.3 +/- 4.2 days. Mild transient lagophthalmos and ptosis were the only complications. Although the exact mechanism of its action and beneficial effect is speculative at this time, botulinum A toxin appears to offer an effective, safe alternative to more radical intracranial surgery for patients with hemifacial spasm.

Temporomandibular Myofacial Pain Treated with Botulinum Toxin Injection

Directory of Open Access Journals (Sweden)

Niv Mor

2015-07-01

Full Text Available This article reviews the diagnoses and treatment of temporomandibular disorders (TMD and outlines of the role of botulinum toxin (BoNT in the treatment of myofacial TMD. This manuscript includes a brief history of the use of BoNT in the treatment of pain, the mechanism of action of BoNT, and the techniques for injections, adverse effects and contraindications when using BoNT to treat mayofacial pain caused by TMD.

Botulinum toxin type A in children and adolescents with severe cerebral palsy: a retrospective chart review.

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Mesterman, Ronit; Gorter, Jan Willem; Harvey, Adrienne; Lockhart, Julia; McEwen-Hill, Jenny; Margallo, Karen; Goldie, Nancy

2014-02-01

This retrospective cohort study reviewed set goals and their outcomes of children and adolescents with severe cerebral palsy who received botulinum toxin A in 2008 and 2009. Sixty children (36 male, mean age 9 years) were included. They received on average 4 (range 1-7) treatments, with the dosage varying between 20 and 400 units per treatment (3-21 U/kg/body weight). Mild transient side effects were reported in 12 of 242 treatments with botulinum toxin A. Treatment goals were related to lower limb function (82%), range of motion (68%), positioning (33%), upper limb function (33%), and facilitating ease of care in dressing (30%), toileting, and diapering (22%). The treatment goals were reached in 60% to 85% by report of the parent and child dyad. Our findings suggest that botulinum toxin A should be considered as a treatment option in patients with cerebral palsy within Gross Motor Function Classification System levels IV and V.

Successful use of botulinum toxin type a in the treatment of refractory postoperative dyspareunia.

Science.gov (United States)

Park, Amy J; Paraiso, Marie Fidela R

2009-08-01

Refractory dyspareunia presents a challenging therapeutic dilemma. A woman with defecatory dysfunction and dyspareunia presented with stage 2 prolapse. She underwent laparoscopic and vaginal pelvic floor reconstruction with excision of endometriosis. The patient experienced increased dyspareunia and de novo vaginismus postoperatively that were refractory to trigger point injections, physical therapy, and medical and surgical management. She underwent botulinum toxin type A injections into her levator ani muscles, which allowed her to have sexual intercourse again after 2 years of apareunia with no recurrence of pain for 12 months. Injecting botulinum toxin into the levator ani muscles shows promise for postoperative patients who develop vaginismus and do not respond to conservative therapy.

The use of botulinum toxin type A in cosmetic facial procedures

NARCIS (Netherlands)

Jaspers, G. W. C.; Pijpe, J.; Jansma, J.

Over the past decade, facial cosmetic procedures have become more commonplace ill dentistry and oral and maxillofacial surgery. An increasing number of patients seek minimal invasive procedures. One of the most requested procedures is treatment with botulinum toxin type A (BoNTA). Treatment of

The medicinal chemistry of botulinum, ricin and anthrax toxins.

Science.gov (United States)

Hicks, Rickey P; Hartell, Mark G; Nichols, Daniel A; Bhattacharjee, Apurba K; van Hamont, John E; Skillman, Donald R

2005-01-01

The potential use of weapons of mass destruction (nuclear, biological or chemical) by terrorist organizations represents a major threat to world peace and safety. Only a limited number of vaccines are available to protect the general population from the medical consequences of these weapons. In addition there are major health concerns associated with a pre-exposure mass vaccination of the general population. To reduce or eliminate the impact of these terrible threats, new drugs must be developed to safely treat individuals exposed to these agents. A review of all therapeutic agents under development for the treatment of the illnesses and injuries that result from exposure to nuclear, biological or chemical warfare agents is beyond the scope of any single article. The intent here is to provide a focused review for medicinal and organic chemists of three widely discussed and easily deployed biological warfare agents, botulinum neurotoxin and ricin toxins and the bacteria Bacillus anthracis. Anthrax will be addressed because of its similarity in both structure and mechanism of catalytic activity with botulinum toxin. The common feature of these three agents is that they exhibit their biological activity via toxin enzymatic hydrolysis of a specific bond in their respective substrate molecules. A brief introduction to the history of each of the biological warfare agents is presented followed by a discussion on the mechanisms of action of each at the molecular level, and a review of current potential inhibitors under investigation.

Botulinum toxin and neuromodulation for overactive bladder treatment

Directory of Open Access Journals (Sweden)

Ramazan Yavuz Akman

2013-03-01

Full Text Available The overactive bladder (OAB is a symptom complex characterized by urgency with /without urge incontinence, and often associated with frequency and nocturia. First-line therapy for OAB includes behavioral therapies and anticholinergic drugs. Although a large number of patients respond to conservative or pharmacological therapy or a combination of the two, some patients are refractory and require additional options for intervention. Botulinum toxin therapy and neuromodulation are frequently used treatment options in refractory OAB patients.

Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature

Science.gov (United States)

2016-08-26

Each neurotoxin subtype within a serotype cleaves its target substrate at the same single conserved peptide bond, except for BoNT/F5 (Table 2) [55...common for strains of C. botulinum Group III to form a chimeric or hybrid protein that combines elements of BoNT/C and BoNT/D neurotoxin, rather than a...Approved for public release; distribution is unlimited. UNCLASSIFIED 15 reported as BoNT/CD or BoNT/DC chimeric toxins [22]. Two exotoxins

Muscle structure and stiffness assessment after botulinum toxin type A injection. A systematic review.

Science.gov (United States)

Mathevon, L; Michel, F; Decavel, P; Fernandez, B; Parratte, B; Calmels, P

2015-12-01

Botulinum toxin type A manages spasticity disorders in neurological central diseases. Some studies have reported that it might induce muscle changes. We present a literature review abiding by the PRISMA statement guidelines. The purpose was to explore the structural and passive biomechanical muscle properties after botulinum toxin type A injections in healthy and spastic limb muscles, on animals and humans, as well as methods for evaluating these properties. We searched the PubMed and Cochrane Library databases using the following keywords: "Botulinum toxin" AND ("muscle structure" OR "muscle atrophy") and, "Botulinum toxin" AND "muscle elasticity". From the 228 initially identified articles, 21 articles were included. Histological analyses were performed, especially on animals. A neurogenic atrophy systematically occurred. In humans, one year after a single injection, the histological recovery remained incomplete. Furthermore, 2D ultrasound analyses showed a reduction of the gastrocnemius thickness and pennation angle. MRI volumetric analysis evidenced muscular atrophy six months or one year after a single injection. Passive muscle stiffness depends on these structural changes. On the short term, the biomechanical analysis showed an elastic modulus increase in animals whereas no change was recorded in humans. On the short term, ultrasound elastography imaging showed a decreased elastic modulus. To date, few data are available, but all show a structural and mechanical muscle impact post injections, specifically muscle atrophy which can linger over time. Further studies are necessary to validate this element, and the possibility of change must be taken into account particularly with repeated injections. Thus, in clinical practice, 2D ultrasound and ultrasound elastography are two non-invasive techniques that will help physicians to develop an efficient long term monitoring. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Genetic homogeneity of Clostridium botulinum type A1 strains with unique toxin gene clusters.

Science.gov (United States)

Raphael, Brian H; Luquez, Carolina; McCroskey, Loretta M; Joseph, Lavin A; Jacobson, Mark J; Johnson, Eric A; Maslanka, Susan E; Andreadis, Joanne D

2008-07-01

A group of five clonally related Clostridium botulinum type A strains isolated from different sources over a period of nearly 40 years harbored several conserved genetic properties. These strains contained a variant bont/A1 with five nucleotide polymorphisms compared to the gene in C. botulinum strain ATCC 3502. The strains also had a common toxin gene cluster composition (ha-/orfX+) similar to that associated with bont/A in type A strains containing an unexpressed bont/B [termed A(B) strains]. However, bont/B was not identified in the strains examined. Comparative genomic hybridization demonstrated identical genomic content among the strains relative to C. botulinum strain ATCC 3502. In addition, microarray data demonstrated the absence of several genes flanking the toxin gene cluster among the ha-/orfX+ A1 strains, suggesting the presence of genomic rearrangements with respect to this region compared to the C. botulinum ATCC 3502 strain. All five strains were shown to have identical flaA variable region nucleotide sequences. The pulsed-field gel electrophoresis patterns of the strains were indistinguishable when digested with SmaI, and a shift in the size of at least one band was observed in a single strain when digested with XhoI. These results demonstrate surprising genomic homogeneity among a cluster of unique C. botulinum type A strains of diverse origin.

Experience with botulinum toxin therapy for axillary hyperhidrosis and comparison to modelled data for endoscopic thoracic sympathectomy - A quality of life and cost effectiveness analysis.

Science.gov (United States)

Gibbons, John P; Nugent, Emmeline; O'Donohoe, Nollaig; Maher, Barry; Egan, Bridget; Feeley, Martin; Tierney, Sean

2016-10-01

To estimate cost-effectiveness of botulinum toxin therapy for axillary hyperhidrosis compared to the standard surgical intervention of endoscopic thoracic sympathectomy (ETS). The validated dermatology life quality index questionnaire was given to patients attending for treatment over a 4 month period, to assess their quality of life (QoL) over the preceding week (n = 44). Follow-up was performed 4-6 weeks later by telephone using the same questionnaire to validate the effectiveness of the treatment. The duration of effect of the botulinum toxin treatment was also recorded and this data was used as the basis for cost effectiveness analysis. Using HIPE data, the baseline cost for single intervention using botulinum toxin and ETS was retrieved. Using figures provided by HIPE and expert opinion of the costs of complications, a stochastic model for 10,000 patients was used to evaluate the total costs for ETS including the complications. The results from the QoL analysis show that botulinum toxin therapy is a successful therapy for improvement of symptoms. It was revealed that the mean interval before recurrence of original symptoms after botulinum toxin therapy was 5.6 months. The baseline cost for both treatments are €389 for botulinum toxin and €9389 for uncomplicated ETS. The stochastic model yields a mean cost of €11,390 for ETS including complications. Treatments reached cost equivalence after 13.3 years. However, given the efficacy of the botulinum toxin therapy and the low risk we propose that botulinum toxin therapy for hyperhidrosis should be considered the gold standard. Copyright © 2015 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

Safety and efficacy of repeated injections of botulinum toxin A in peripheral neuropathic pain (BOTNEP): a randomised, double-blind, placebo-controlled trial.

Science.gov (United States)

Attal, Nadine; de Andrade, Daniel C; Adam, Frédéric; Ranoux, Danièle; Teixeira, Manoel J; Galhardoni, Ricardo; Raicher, Irina; Üçeyler, Nurcan; Sommer, Claudia; Bouhassira, Didier

2016-05-01

Data from previous studies suggest that botulinum toxin A has analgesic effects against peripheral neuropathic pain, but the quality of the evidence is low. We aimed to assess the safety and efficacy of repeated administrations of botulinum toxin A in patients with neuropathic pain. We did a randomised, double-blind, placebo-controlled trial at two outpatient clinics in France (Clinical Pain Centre, Ambroise Paré Hospital, APHP, Boulogne-Billancourt, and Neurological Centre, Hôpital Dupuytren, Limoges) and one in Brazil (Neurological Department, Hospital das Clínicas da FMUSP, São Paulo). Patients aged 18-85 years with peripheral neuropathic pain were randomly assigned (1:1) by block randomisation, according to a centralised schedule, to receive two subcutaneous administrations of botulinum toxin A (up to 300 units) or placebo, 12 weeks apart. All patients and investigators were masked to treatment assignment. The primary outcome was the efficacy of botulinum toxin A versus placebo, measured as the change from baseline in self-reported mean weekly pain intensity over the course of 24 weeks from the first administration. The primary efficacy analysis was a mixed-model repeated-measures analysis in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01251211. Between Oct 2, 2010, and Aug 2, 2013, 152 patients were enrolled, of whom 68 were randomly assigned (34 per group), and 66 (37 [56%] men) were included in the primary analysis (34 in the botulinum toxin A group and 32 in the placebo group). Botulinum toxin A reduced pain intensity over 24 weeks compared with placebo (adjusted effect estimate -0·77, 95% CI -0·95 to -0·59; pbotulinum toxin A group and 17 (53%) of those in the placebo group (p=1·0). Severe pain was experienced by ten (29%) participants in the botulinum toxin A group and 11 (34%) in the placebo group (p=0·8). Two administrations of botulinum toxin A, each of which comprised several injections, have a

Botulinum toxin injection causes hyper-reflexia and increased muscle stiffness of the triceps surae muscle in the rat

OpenAIRE

Pingel, Jessica; Wienecke, Jacob; Lorentzen, Jakob; Nielsen, Jens Bo

2016-01-01

This study demonstrates, for the first time, adaptive plastic changes in the stretch reflex circuitry following denervation induced by botulinum toxin injection. The study also demonstrates alterations of the elastic properties of the muscles following botulinum injection.

Antagonism of botulinum toxin-induced muscle weakness by aminopyridines in rat phrenic nerve-hemidiaphragm preparations

Energy Technology Data Exchange (ETDEWEB)

Adler, M.; Scovill, J.; Deshpande, S.S.

1993-05-13

The effects of the potassium channel inhibitor and putative botulinum toxin antagonists 4-aminopyridine (4-AP) and 3,4-diaminopyridine (3,4-DAP) were investigated in vitro on the contractile and electrophysiological properties of rat diaphragm muscle. In the presence of 300 pM botulinum toxin A (BoTx A), twitches elicited by supramaximal nerve stimulation (0. 1 Hz) were reduced by over 80% in 3 hr. The time to block decreased with increases in temperature, toxin concentration and stimulation frequency. Addition of 4-AP or 3,4-DAP led to a prompt reversal of the BoTx A-induced depression of twitch tension. This reversal was concentration-dependent such that, in the presence of 1 mM 4-AP, reversal of the BoTx A-induced blockade was complete in 6.7 min. The beneficial effect of the APs were well maintained and persisted for up to 6 hr after addition. Application of 1 microns M neostigmine 1 hr after 3,4-DAP produced a further potentiation of twitch tensions, but this action lasted for < 5 min and led to the appearance of tetanic fade during repetitive stimulation. It is concluded that the APs are of benefit in antagonizing the muscle paralysis following exposure to botulinum toxin. Co-application of neostigmine, however, appears to confer no additional benefit.

Mechano- and metabosensitive alterations after injection of botulinum toxin into gastrocnemius muscle.

Science.gov (United States)

Caron, Guillaume; Rouzi, Talifujiang; Grelot, Laurent; Magalon, Guy; Marqueste, Tanguy; Decherchi, Patrick

2014-07-01

This study was designed to investigate effects of motor denervation by Clostridium botulinum toxin serotype A (BoNT/A) on the afferent activity of fibers originating from the gastrocnemius muscle of rats. Animals were randomized in two groups, 1) untreated animals acting as control and 2) treated animals in which the toxin was injected in the left muscle. Locomotor activity was evaluated once per day during 12 days with a test based on footprint measurements of walking rats (sciatic functional index). At the end of the functional assessment period, electrophysiological tests were used to measure muscle properties, metabosensitive afferent fiber responses to chemical (KCl and lactic acid) injections, electrically induced fatigue (EIF), and mechanosensitive responses to tendon vibrations. Additionally, ventilatory response was recorded during repetitive muscle contractions. Then, rats were sacrificed, and the BoNT/A-injected muscles were weighed. Twelve days postinjection we observed a complete motor denervation associated with a significant muscle atrophy and loss of force to direct muscle stimulation. In the BoNT/A group, the metabosensitive responses to KCl injections were unaltered. However, we observed alterations in responses to EIF and to 1 mM of lactic acid (which induces the greatest activation). The ventilatory adjustments during repetitive muscle activation were abolished, and the mechanosensitive fiber responses to tendon vibrations were reduced. These results indicate that BoNT/A alters the sensorimotor loop and may induce insufficient motor and physiological adjustments in patients in whom a motor denervation with BoNT/A was performed. Copyright © 2014 Wiley Periodicals, Inc.

Effect of headspace CO2 concentration on toxin production by Clostridium botulinum in MAP, irradiated fresh pork

International Nuclear Information System (INIS)

Lambert, A.D.; Smith, J.P.; Dodds, K.L.

1991-01-01

The effects of five initial levels of CO2 (15, 30, 45, 60, and 75%) and three irradiation doses (0, 0.5, and 1.0 kGy) on toxin production by Clostridium botulinum in inoculated fresh pork were studied using factorial design experiments. Headspace CO2 levels increased in all samples during storage at 15 degrees C. In most treatments, spoilage preceded toxigenesis. Toxin production occurred faster in samples initially packaged with 15 to 30% of CO2 while higher levels of CO2 (45-75%) delayed toxin production. Low-dose irradiation delayed toxin production at all levels of CO2 in the package headspace. Contrary to expectations, including a CO2 absorbent in the package enhanced toxin production by C. botulinum. This was attributed to production of H2 by the CO2 absorbent, possibly resulting in a decrease in the oxido-reduction potential of the meat

In situ detection of the Clostridium botulinum type C1 toxin gene in wetland sediments with a nested PCR assay

Science.gov (United States)

Williamson, Judy L.; Rocke, Tonie E.; Aiken, Judd M.

1999-01-01

A nested PCR was developed for detection of the Clostridium botulinum type C1 toxin gene in sediments collected from wetlands where avian botulism outbreaks had or had not occurred. The C1 toxin gene was detected in 16 of 18 sites, demonstrating both the ubiquitous distribution of C. botulinum type C in wetland sediments and the sensitivity of the detection assay.

[Applications of botulinum toxin in Neurology].

Science.gov (United States)

Garcia-Ruiz, Pedro J

2013-07-07

At present, botulinum toxin (BT) is one of the most fundamental available drugs in Neurology, only comparable with levodopa. BT is currently used in those entities characterized by excessive muscle contraction, including dystonia and spasticity. In addition, BT has been used to control pain associated with increased muscle contraction in dystonia and spasticity, but also is useful to control chronic pain not associated with muscle contraction, such as chronic daily headache. Finally, BT is useful in sialorrhoea and bruxism. The mechanism of action is complex, mainly acting on terminal neuromuscular junction, but also exhibiting analgesic properties, probably through inhibition of pain neurotransmitters release. Copyright © 2012 Elsevier España, S.L. All rights reserved.

In vitro reconstitution of the Clostridium botulinum type D progenitor toxin.

Science.gov (United States)

Kouguchi, Hirokazu; Watanabe, Toshihiro; Sagane, Yoshimasa; Sunagawa, Hiroyuki; Ohyama, Tohru

2002-01-25

Clostridium botulinum type D strain 4947 produces two different sizes of progenitor toxins (M and L) as intact forms without proteolytic processing. The M toxin is composed of neurotoxin (NT) and nontoxic-nonhemagglutinin (NTNHA), whereas the L toxin is composed of the M toxin and hemagglutinin (HA) subcomponents (HA-70, HA-17, and HA-33). The HA-70 subcomponent and the HA-33/17 complex were isolated from the L toxin to near homogeneity by chromatography in the presence of denaturing agents. We were able to demonstrate, for the first time, in vitro reconstitution of the L toxin formed by mixing purified M toxin, HA-70, and HA-33/17. The properties of reconstituted and native L toxins are indistinguishable with respect to their gel filtration profiles, native-PAGE profiles, hemagglutination activity, binding activity to erythrocytes, and oral toxicity to mice. M toxin, which contained nicked NTNHA prepared by treatment with trypsin, could no longer be reconstituted to the L toxin with HA subcomponents, whereas the L toxin treated with proteases was not degraded into M toxin and HA subcomponents. We conclude that the M toxin forms first by assembly of NT with NTNHA and is subsequently converted to the L toxin by assembly with HA-70 and HA-33/17.

Effect of Equilibrated pH and Indigenous Spoilage Microorganisms on the Inhibition of Proteolytic Clostridium botulinum Toxin Production in Experimental Meals under Temperature Abuse.

Science.gov (United States)

Golden, Max C; Wanless, Brandon J; David, Jairus R D; Lineback, D Scott; Talley, Ryan J; Kottapalli, Bala; Glass, Kathleen A

2017-08-01

Clostridium botulinum is a foreseeable biological hazard in prepared refrigerated meals that needs to be addressed in food safety plans. The objective of this study was to evaluate the effect of product composition and storage temperature on the inhibition of botulinum toxin formation in nine experimental meals (meat, vegetable, or carbohydrate based). Treatments were inoculated with proteolytic C. botulinum, vacuum packaged, cooked at 90°C for 10 min, and assayed for botulinum toxin in samples stored at 25°C for up to 96 h for phase 1, or at 25°C for 12 h and then transferred to 12.5°C for up to 12 and 6 weeks in phases 1 and 2, respectively. For phase 1, none of the treatments (equilibrated pH 5.8) supported toxin production when stored at 25°C for 48 h, but toxin production was observed in all treatments at 72 h. For the remaining experiments with storage at 12.5°C, toxin production was dependent on equilibrated pH, storage time, and growth of indigenous spoilage microorganisms. In phase 1, no gross spoilage and no botulinum toxin was detected for any treatment (pH ≤5.8) stored at 12.5°C for 12 weeks. In phase 2, gross spoilage varied by commodity, with the brussels sprouts meal with pH 6.5 showing the most rapid spoilage within 2 weeks and botulinum toxin detected at 5 and 6 weeks for the control and cultured celery juice treatments, respectively. In contrast, spoilage microbes decreased the pH of a pH 5.9 beef treatment by 1.0 unit, potentially inhibiting C. botulinum through 6 weeks at 12.5°C. None of the other treatments with pH 5.8 or below supported toxin production or spoilage. This study provides validation for preventive controls in refrigerated meals. These include equilibrated product pH and storage temperature and time to inhibit toxin formation by proteolytic C. botulinum, but the impact of indigenous microflora on safety and interpretation of challenge studies is also highlighted.

Diffusion, spread, and migration of botulinum toxin.

Science.gov (United States)

Ramirez-Castaneda, Juan; Jankovic, Joseph; Comella, Cynthia; Dashtipour, Khashayar; Fernandez, Hubert H; Mari, Zoltan

2013-11-01

Botulinum toxin (BoNT) is an acetylcholine release inhibitor and a neuromuscular blocking agent used for the treatment of a variety of neurologic and medical conditions. The efficacy and safety of BoNT depends on accurate selection and identification of intended targets but also may be determined by other factors, including physical spread of the molecule from the injection site, passive diffusion, and migration to distal sites via axonal or hematogenous transport. The passive kinetic dispersion of the toxin away from the injection site in a gradient-dependent manner may also play a role in toxin spread. In addition to unique properties of the various BoNT products, volume and dilution may also influence local and systemic distribution of BoNT. Most of the local and remote complications of BoNT injections are thought to be due to unwanted spread or diffusion of the toxin's biologic activity into adjacent and distal muscles. Despite widespread therapeutic and cosmetic use of BoNT over more than three decades, there is a remarkable paucity of published data on the mechanisms of distribution and its effects on clinical outcomes. The primary aim of this article is to critically review the available experimental and clinical literature and place it in the practical context. © 2013 International Parkinson and Movement Disorder Society.

Influence of Botulinum Toxin Therapy on Postural Control and Lower Limb Intersegmental Coordination in Children with Spastic Cerebral Palsy

Directory of Open Access Journals (Sweden)

Bernard Dan

2013-01-01

Full Text Available Botulinum toxin injections may significantly improve lower limb kinematics in gait of children with spastic forms of cerebral palsy. Here we aimed to analyze the effect of lower limb botulinum toxin injections on trunk postural control and lower limb intralimb (intersegmental coordination in children with spastic diplegia or spastic hemiplegia (GMFCS I or II. We recorded tridimensional trunk kinematics and thigh, shank and foot elevation angles in fourteen 3–12 year-old children with spastic diplegia and 14 with spastic hemiplegia while walking either barefoot or with ankle-foot orthoses (AFO before and after botulinum toxin infiltration according to a management protocol. We found significantly greater trunk excursions in the transverse plane (barefoot condition and in the frontal plane (AFO condition. Intralimb coordination showed significant differences only in the barefoot condition, suggesting that reducing the degrees of freedom may limit the emergence of selective coordination. Minimal relative phase analysis showed differences between the groups (diplegia and hemiplegia but there were no significant alterations unless the children wore AFO. We conclude that botulinum toxin injection in lower limb spastic muscles leads to changes in motor planning, including through interference with trunk stability, but a combination of therapies (orthoses and physical therapy is needed in order to learn new motor strategies.

Structure, Function and Evolution of Clostridium botulinum C2 and C3 Toxins: Insight to Poultry and Veterinary Vaccines.

Science.gov (United States)

Chellapandi, Paulchamy; Prisilla, Arokiyasamy

2017-01-01

Clostridium botulinum group III strains are able to produce cytotoxins, C2 toxin and C3 exotoxin, along with botulinum neurotoxin types C and D. C2 toxin and C3 exotoxin produced by this organism are the most important members of bacterial ADP-ribosyltransferase superfamily. Both toxins have distinct pathophysiological functions in the avian and mammalian hosts. The members of this superfamily transfer an ADP-ribose moiety of NAD+ to specific eukaryotic target proteins. The present review describes the structure, function and evolution aspects of these toxins with a special emphasis to the development of veterinary vaccines. C2 toxin is a binary toxin that consists of a catalytic subunit (C2I) and a translocation subunit (C2II). C2I component is structurally and functionally similar to the VIP2 and iota A toxin whereas C2II component shows a significant homology with the protective antigen from anthrax toxin and iota B. Unlike C2 toxin, C3 toxin is devoid of translocation/binding subunit. Extensive studies on their sequence-structure-function link spawn additional efforts to understand the catalytic mechanisms and target recognition. Structural and functional relationships with them are often determined by using evolutionary constraints as valuable biological measures. Enzyme-deficient mutants derived from these toxins have been used as drug/protein delivery systems in eukaryotic cells. Thus, current knowledge on their molecular diversity is a well-known perspective to design immunotoxin or subunit vaccine for C. botulinum infection. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Combined Effect Of Botulinum Toxin And Splinting On Motor Components And Function Of People With Stroke

Directory of Open Access Journals (Sweden)

Aryan Shamili

2017-02-01

Full Text Available Background and objective: Spasticity is one of the problems following stroke. Due to this increase in muscle tone, patients are confronted to problems in motor control and difficulties in activities of daily living and complications such as shortness and contracture. The aim of this study was to examine the effects of Simultaneous use of both splint and botulinum toxin-A (BTX-A injection on spasticity, range of motion and upper extremity function in a 3-month period. Methods: The design of this study was a comparison between 3 groups of interventions, conducted in rehabilitation clinics in Tehran. Sixty people with chronic stroke were recruited. Based on the inclusion criteria, a total of 39 stroke patients after completing the consent forms were entered to intervention groups; splint or botulinum toxin injection or combined splint/botulinum toxin injection. They were followed up about 3 months and the evaluations were done monthly. Goniometry was the method to measure range of motion, and Modified Ashworth scale was used to examine the spasticity and the upper extremity function was scored based on Fugl-Meyer assessment.   Statistical analysis was done using SPSS 17. And ANOVAs was used for comparison between groups and times.  Significance was set at 0.05. Results: All outcome measures improved within each group but the differences between splint group and BTX-A group and the BTX-A-splint group was not significant in most outcomes during 3 periods (first evaluation until end of the first month, the end of first month until the end of second month, the end of second month until the end of the third month (p> 0 / 05. The results also showed that the changes in elbow`s spasticity {p= 0.05} and wrist`s spasticity {p= 0.007} and upper extremity function { p = 0.04} were obvious between the three groups over the 3-months and the difference in the group of combined use of botulinum toxin and splint was more than other groups. Conclusion: In this

Thickened saliva after effective management of drooling with botulinum toxin A

NARCIS (Netherlands)

Erasmus, C.E.; van Hulst, K.; van den Hoogen, F.J.; van Limbeek, J.; Roeleveld, N.; Veerman, E.C.I.; Rotteveel, J.J.; Jongerius, P.H.

2010-01-01

Aim: The aim of this study was to evaluate the rheological properties of saliva after submandibular botulinum toxin type A (BoNT-A) injections. Method: We enrolled 15 children (11 males and six females; age range 3-17y, mean age 9y 10mo) diagnosed with spastic (n=9) or dyskinetic (n=6) quadriplegic

Thickened saliva after effective management of drooling with botulinum toxin A.

NARCIS (Netherlands)

Erasmus, C.E.; Hulst, K. van; Hoogen, F.J.A. van den; Limbeek, J. van; Roeleveld, N.; Veerman, E.C.; Rotteveel, J.J.; Jongerius, P.H.

2010-01-01

AIM: The aim of this study was to evaluate the rheological properties of saliva after submandibular botulinum toxin type A (BoNT-A) injections. METHOD: We enrolled 15 children (11 males and six females; age range 3-17 y, mean age 9 y 10 mo) diagnosed with spastic (n=9) or dyskinetic (n=6)

Association of toxin-producing Clostridium botulinum with the macroalga Cladophora in the Great Lakes.

Science.gov (United States)

Chun, Chan Lan; Ochsner, Urs; Byappanahalli, Muruleedhara N; Whitman, Richard L; Tepp, William H; Lin, Guangyun; Johnson, Eric A; Peller, Julie; Sadowsky, Michael J

2013-03-19

Avian botulism, a paralytic disease of birds, often occurs on a yearly cycle and is increasingly becoming more common in the Great Lakes. Outbreaks are caused by bird ingestion of neurotoxins produced by Clostridium botulinum, a spore-forming, gram-positive, anaerobe. The nuisance, macrophytic, green alga Cladophora (Chlorophyta; mostly Cladophora glomerata L.) is a potential habitat for the growth of C. botulinum. A high incidence of botulism in shoreline birds at Sleeping Bear Dunes National Lakeshore (SLBE) in Lake Michigan coincides with increasingly massive accumulations of Cladophora in nearshore waters. In this study, free-floating algal mats were collected from SLBE and other shorelines of the Great Lakes between June and October 2011. The abundance of C. botulinum in algal mats was quantified and the type of botulism neurotoxin (bont) genes associated with this organism were determined by using most-probable-number PCR (MPN-PCR) and five distinct bont gene-specific primers (A, B, C, E, and F). The MPN-PCR results showed that 16 of 22 (73%) algal mats from the SLBE and 23 of 31(74%) algal mats from other shorelines of the Great Lakes contained the bont type E (bont/E) gene. C. botulinum was present up to 15000 MPN per gram dried algae based on gene copies of bont/E. In addition, genes for bont/A and bont/B, which are commonly associated with human diseases, were detected in a few algal samples. Moreover, C. botulinum was present as vegetative cells rather than as dormant spores in Cladophora mats. Mouse toxin assays done using supernatants from enrichment of Cladophora containing high densities of C. botulinum (>1000 MPN/g dried algae) showed that Cladophora-borne C. botulinum were toxin-producing species (BoNT/E). Our results indicate that Cladophora provides a habitat for C. botulinum, warranting additional studies to better understand the relationship between this bacterium and the alga, and how this interaction potentially contributes to botulism

Clostridium botulinum C2 toxin--new insights into the cellular up-take of the actin-ADP-ribosylating toxin.

Science.gov (United States)

Aktories, Klaus; Barth, Holger

2004-04-01

Clostridium botulinum C2 toxin is a member of the family of binary actin-ADP-ribosylating toxins. It consists of the enzyme component C2I, and the separated binding/translocation component C2II. Proteolytically activated C2II forms heptamers and binds to a carbohydrate cell surface receptor. After attachment of C2I, the toxin complex is endocytosed to reach early endosomes. At low pH of endosomes, C2II-heptamers insert into the membrane, form pores and deliver C2I into the cytosol. Here, C2I ADP-ribosylates actin at Arg177 to block actin polymerization and to induce depolymerization of actin filaments. The mini-review describes main properties of C2 toxin and discusses new findings on the involvement of chaperones in the up-take process of the toxin.

Effect of botulinum toxin for eyelid retraction in dysthyroid ophthalmopathy as related to hypertrophy of intraorbital muscles

International Nuclear Information System (INIS)

Komoto, Noriko; Kozaki, Ai; Yu, Fumihiko; Inoue, Rishu; Maeda, Toshine; Inoue, Toyoko; Inoue, Yoichi

2007-01-01

The purpose of this study was to report the effect of botulinum toxin for eyelid retraction in dysthyroid ophthalmopathy with or without hypertrophy of intraorbital muscles. We reviewed 28 eyes of 23 cases who received injection of botulinum toxin for eyelid retraction. Eyelid retraction improved in 23 eyes (82%). The height of palpebral fissure ranged from 8 to 12 mm, average 10.8 mm, before treatment. It ranged from 5 to 12 mm, average 9.4 mm, 2 weeks after treatment. The difference was significant. By magnetic resonance imaging (MRI), hypertrophy of levator and/or superior rectus muscle was present in 19 eyes and absent in 9 eyes. Eyelid retraction improved in 2 eyes (11%) in the former group and in one eye (11%) in the latter. Dalrymple sign was present in 28 eyes before and disappeared in 14 eyes after treatment. Graefe sign was present in 28 eyes before and disappeared in one eye after treatment. Botulinum toxin is effective for eyelid retraction and not for Graefe sign in dysthyroid ophthalmopathy. (author)

Effect of Botulinum Toxin and Surgery among Spasmodic Dysphonia Patients : A Systematic Review

NARCIS (Netherlands)

van Esch, Babette F; Wegner, Inge; Stegeman, Inge; Grolman, Wilko

2017-01-01

OBJECTIVE: The effect of botulinum toxin among patients with adductor spasmodic dysphonia (AdSD) is temporary. To optimize long-term treatment outcome, other therapy options should be evaluated. Alternative treatment options for AdSD comprise several surgical treatments, such as thyroarytenoid

Office-based Electromyography-guided Botulinum Toxin Injection to the Cricopharyngeus Muscle: Optimal Patient Selection and Technique.

Science.gov (United States)

Kim, Min-Su; Kim, Go-Woon; Rho, Young-Soo; Kwon, Kee-Hwan; Chung, Eun-Jae

2017-05-01

This retrospective study was carried out to investigate the effectiveness and safety of office-based electromyography-guided injection of botulinum toxin in the cricopharyngeus muscle of patients who did not show upper esophageal sphincter passage in a swallowing study in spite of maximal swallowing rehabilitation. Thirty-six patients who showed no or limited ability to oral feed after maximum swallowing rehabilitation were enrolled. Video fluoroscopic swallowing study, flexible endoscopic evaluation of swallowing, disability rating scale, penetration aspiration score, and National Institutes of Health swallowing safety scale were used in the evaluation of dysphagia. Success was defined as nondependence on gastrostomy for patients who previously were dependent on gastrostomy and improvement in disability rating scale score after botulinum toxin injections. The total success rate was 63.9%. The complication rate was very low, with only 1 patient showing temporary unilateral vocal fold paralysis. Botulinum toxin injection was more effective in patients with cranial nerve IX or X palsy than in those without it ( P = .006). This procedure can be a simple, safe, and effective tool in patients with cricopharyngeal dysfunction after swallowing rehabilitation, especially for cranial nerve IX or X palsy.

Botulinum Toxin A as an Adjunct to Abdominal Wall Reconstruction for Incisional Hernia

DEFF Research Database (Denmark)

Soltanizadeh, Sinor; Helgstrand, Frederik; Jorgensen, Lars N

2017-01-01

BACKGROUND: Repair of large incisional hernias remains a surgical and costly challenge. Temporary paralysis of the lateral abdominal wall muscles with topical administration of botulinum toxin A (BTA) is a new therapeutic concept, which may obviate the need for component separation technique (CST...

Inhibition of Metalloprotease Botulinum Serotype A from a Pseudo-Peptide Binding Mode to a Small Molecule that is Active in Primary Neurons

National Research Council Canada - National Science Library

Burnett, James C; Ruthel, Gordon; Stegmann, Christian M; Panchal, Rekha G; Nguyen, Tam L; Hermone, Ann R; Stafford, Robert G; Lane, Douglas J; Kenny, Tara A; McGarth, Connor F

2007-01-01

An efficient research strategy integrating empirically-guided, structure-based modeling and chemoinformatics was used to discover potent small molecule inhibitors of the botulinum neurotoxin serotype A light chain...

Flagellar glycosylation in Clostridium botulinum.

Science.gov (United States)

Twine, Susan M; Paul, Catherine J; Vinogradov, Evgeny; McNally, David J; Brisson, Jean-Robert; Mullen, James A; McMullin, David R; Jarrell, Harold C; Austin, John W; Kelly, John F; Logan, Susan M

2008-09-01

Flagellins from Clostridium botulinum were shown to be post-translationally modified with novel glycan moieties by top-down MS analysis of purified flagellin protein from strains of various toxin serotypes. Detailed analyses of flagellin from two strains of C. botulinum demonstrated that the protein is modified by a novel glycan moiety of mass 417 Da in O-linkage. Bioinformatic analysis of available C. botulinum genomes identified a flagellar glycosylation island containing homologs of genes recently identified in Campylobacter coli that have been shown to be responsible for the biosynthesis of legionaminic acid derivatives. Structural characterization of the carbohydrate moiety was completed utilizing both MS and NMR spectroscopy, and it was shown to be a novel legionaminic acid derivative, 7-acetamido-5-(N-methyl-glutam-4-yl)-amino-3,5,7,9-tetradeoxy-D-glycero-alpha-D-galacto-nonulosonic acid, (alphaLeg5GluNMe7Ac). Electron transfer dissociation MS with and without collision-activated dissociation was utilized to map seven sites of O-linked glycosylation, eliminating the need for chemical derivatization of tryptic peptides prior to analysis. Marker ions for novel glycans, as well as a unique C-terminal flagellin peptide marker ion, were identified in a top-down analysis of the intact protein. These ions have the potential for use in for rapid detection and discrimination of C. botulinum cells, indicating botulinum neurotoxin contamination. This is the first report of glycosylation of Gram-positive flagellar proteins by the 'sialic acid-like' nonulosonate sugar, legionaminic acid.

The use of botulinum toxin in head and face medicine: An interdisciplinary field

Directory of Open Access Journals (Sweden)

Laskawi Rainer

2008-03-01

Full Text Available Abstract Background In this review article different interdisciplinary relevant applications of botulinum toxin type A (BTA in the head and face region are demonstrated. Patients with head and face disorders of different etiology often suffer from disorders concerning their musculature (example: synkinesis in mimic muscles or gland-secretion. This leads to many problems and reduces their quality of life. The application of BTA can improve movement disorders like blepharospasm, hemifacial spasm, synkinesis following defective healing of the facial nerve, palatal tremor, severe bruxism, oromandibular dystonias hypertrophy of the masseter muscle and disorders of the autonomous nerve system like hypersalivation, hyperlacrimation, pathological sweating and intrinsic rhinitis. Conclusion The application of botulinum toxin type A is a helpful and minimally invasive treatment option to improve the quality of life in patients with head and face disorders of different quality and etiology. Side effects are rare.

Comparison of Efficacy and Side Effects of Oral Baclofen Versus Tizanidine Therapy with Adjuvant Botulinum Toxin Type A in Children With Cerebral Palsy and Spastic Equinus Foot Deformity.

Science.gov (United States)

Dai, Alper I; Aksoy, Sefika N; Demiryürek, Abdullah T

2016-02-01

This retrospective study aimed to compare the therapeutic response, including side effects, for oral baclofen versus oral tizanidine therapy with adjuvant botulinum toxin type A in a group of 64 pediatric patients diagnosed with static encephalopathy and spastic equinus foot deformity. Following botulinum toxin A treatment, clinical improvement led to the gradual reduction of baclofen or tizanidine dosing to one-third of the former dose. Gross Motor Functional Measure and Caregiver Health Questionnaire scores were markedly elevated post-botulinum toxin A treatment, with scores for the tizanidine (Gross Motor Functional Measure: 74.45 ± 3.72; Caregiver Health Questionnaire: 72.43 ± 4.29) group significantly higher than for the baclofen group (Gross Motor Functional Measure: 68.23 ± 2.66; Caregiver Health Questionnaire: 67.53 ± 2.67, P botulinum toxin A and a low dose of tizanidine in treating children with cerebral palsy appears to be more effective and has fewer side effects versus baclofen with adjuvant botulinum toxin A. © The Author(s) 2015.

Treatment of severe drooling with botulinum toxin in amyotrophic lateral sclerosis and Parkinson's disease: Efficacy and possible mechanisms

DEFF Research Database (Denmark)

Møller, Eigild; Karlsborg, Merete; Jensen, Allan Bardow

2011-01-01

Drooling in neurodegenerative diseases is associated with social impediment. Previous treatments of drooling have little effect or are effective but with severe side effects. Therefore, there is a need to test new methods such as the use of botulinum toxin type A (BTX-A).......Drooling in neurodegenerative diseases is associated with social impediment. Previous treatments of drooling have little effect or are effective but with severe side effects. Therefore, there is a need to test new methods such as the use of botulinum toxin type A (BTX-A)....

Use of anatomic measurement to guide injection of botulinum toxin for the management of chronic lateral epicondylitis: a randomized controlled trial

Science.gov (United States)

Espandar, Ramin; Heidari, Pedram; Rasouli, Mohammad Reza; Saadat, Soheil; Farzan, Mahmood; Rostami, Mohsen; Yazdanian, Shideh; Mortazavi, S.M. Javad

2010-01-01

Background When using botulinum toxin for the management of lateral epicondylitis, injection at a fixed distance from an anatomic landmark could result in inadequate paralysis of the intended muscle. We assessed the effectiveness of injection of botulinum toxin using precise anatomic measurement in individual patients. Methods In this randomized placebo-controlled trial, 48 patients with chronic refractory lateral epicondylitis were randomly assigned to receive a single injection of either botulinum toxin (60 units) or placebo (normal saline). The site of injection was chosen as a distance one-third the length of the forearm from the tip of the lateral epicondyle on the course of the posterior interosseus nerve. The primary outcome measure was intensity of pain at rest, measured with the use of a 100-mm visual analogue scale, at baseline and at 4, 8 and 16 weeks after injection. Results Compared with the placebo group, the group given botulinum toxin had significant reductions in pain at rest during follow-up (decrease at 4 weeks 14.1 mm, 95% confidence interval [CI] 5.8–22.3; at 8 weeks 11.5 mm, 95% CI 2.0–21.0; at 16 weeks 12.6 mm, 95% CI 7.7–17.8; p = 0.01). As for the secondary outcomes, the intensity of pain during maximum pinch decreased in the botulinum toxin group; there was no difference in pain during maximum grip or in grip strength between the two groups. All but one of the patients in the intervention group experienced weakness in the extension of the third and fourth fingers at week 4 that resolved by week 16. No serious adverse events were reported. Interpretation The use of precise anatomic measurement to guide injection of botulinum toxin significantly reduced pain at rest in patients with chronic refractory lateral epicondylitis. However, the transient extensor lag makes this method inappropriate for patients whose job requires finger extension. (ClinicalTrials.gov trial register no. NCT00497913.) PMID:20421357

Kinetic and Reaction Pathway Analysis in the Application of Botulinum Toxin A for Wound Healing

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Frank J. Lebeda

2012-01-01

Full Text Available A relatively new approach in the treatment of specific wounds in animal models and in patients with type A botulinum toxin is the focus of this paper. The indications or conditions include traumatic wounds (experimental and clinical, surgical (incision wounds, and wounds such as fissures and ulcers that are signs/symptoms of disease or other processes. An objective was to conduct systematic literature searches and take note of the reactions involved in the healing process and identify corresponding pharmacokinetic data. From several case reports, we developed a qualitative model of how botulinum toxin disrupts the vicious cycle of muscle spasm, pain, inflammation, decreased blood flow, and ischemia. We transformed this model into a minimal kinetic scheme for healing chronic wounds. The model helped us to estimate the rate of decline of this toxin's therapeutic effect by calculating the rate of recurrence of clinical symptoms after a wound-healing treatment with this neurotoxin.

Botulinum as a Toxin for Treating Post-herpetic Neuralgia

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DING, Xu-Dong; ZHONG, Jing; LIU, Yan-Ping; CHEN, Hua-Xian

2017-01-01

Background: We aimed to study the curative effects of botulinum A toxin (BTX-A) on the treatment of post-herpetic neuralgia (PNH). Methods: We enrolled 58 PNH patients and treated them with hypodermic injection of BTX-A in Xiangyang No.1 People?s Hospital, Hubei University of Medicine, Hubei, China. We measured and compared the Visual Analog Score (VAS), Neuropathy Pain Scale (NPS), Quality of Life Scale (SF-36) score, PNH seizure severity degree, seizure duration, frequency of attack and the...

Botulinum toxin uses in strabismus: A review of the injections performed during one year in a general hospital.

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Jarrín, E; Arranz Márquez, E; Yebra González, L; García Gil de Bernabé, J

2016-03-01

To analyse the indications, dosage and efficacy of botulinum toxin A injection performed in patients in a Strabismus Department. In this prospective study, botulinum toxin A was injected into 28 patients diagnosed with strabismus. Data was obtained from the records of patients that were evaluated during 2013 in the Strabismus Unit of Rey Juan Carlos Hospital (Móstoles, Madrid, Spain) in order to assess the indications and dosage of botulinum toxin A use in strabismus, as well as its clinical effect and differences in paediatric and adult patients. The outcomes in the last visit, at least 14 months after the injections, were analysed. An analysis was performed on the data from 11 children, 6 females (54.5%), and 17 adults, 11 males (64%). The mean age was 4.42±3.48 years and 58.71±18.07 years in the children and adult groups, respectively. The majority of cases in both groups were esotropia (81.8% in children and 47.1% in adults). However the pathologies in the adult group were quite heterogeneous, including 4 patients with exotropia (26.5%), 4 with hypertropia (26.5%), and one with isolated nystagmus (5.9%). The mean number of the botulinum toxin injections in children was 1.45±0.93, although 72.7% received a single injection. In the adult group, the mean number of injections was 3.27±1.41. There was a statistically significant difference between pre- and post-injection in the tropia and phoria measurements in children and adults group (Ptoxin injection, whereas 2 needed surgery for diplopia correction. Botulinum toxin is a very useful tool in the management of strabismus, obtaining better sensory and motor results in children, but it is also effective as a symptomatic treatment in some types of strabismus in adults. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Thickened Saliva after Effective Management of Drooling with Botulinum Toxin A

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Erasmus, Corrie E.; van Hulst, Karen; van den Hoogen, Frank J. A.; van Limbeek, Jacques; Roeleveld, Nel; Veerman, Enno C. I.; Rotteveel, Jan J.; Jongerius, Peter H.

2010-01-01

Aim: The aim of this study was to evaluate the rheological properties of saliva after submandibular botulinum toxin type A (BoNT-A) injections. Method: We enrolled 15 children (11 males and six females; age range 3-17y, mean age 9y 10mo) diagnosed with spastic (n=9) or dyskinetic (n=6) quadriplegic cerebral palsy (CP); Gross Motor Function…

Quantitative determination of biological activity of botulinum toxins utilizing compound muscle action potentials (CMAP), and comparison of neuromuscular transmission blockage and muscle flaccidity among toxins.

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Torii, Yasushi; Goto, Yoshitaka; Takahashi, Motohide; Ishida, Setsuji; Harakawa, Tetsuhiro; Sakamoto, Takashi; Kaji, Ryuji; Kozaki, Shunji; Ginnaga, Akihiro

2010-01-01

The biological activity of various types of botulinum toxin has been evaluated using the mouse intraperitoneal LD(50) test (ip LD(50)). This method requires a large number of mice to precisely determine toxin activity, and so has posed a problem with regard to animal welfare. We have used a direct measure of neuromuscular transmission, the compound muscle action potential (CMAP), to evaluate the effect of different types of botulinum neurotoxin (NTX), and we compared the effects of these toxins to evaluate muscle relaxation by employing the digit abduction scoring (DAS) assay. This method can be used to measure a broad range of toxin activities the day after administration. Types A, C, C/D, and E NTX reduced the CMAP amplitude one day after administration at below 1 ip LD(50), an effect that cannot be detected using the mouse ip LD(50) assay. The method is useful not only for measuring toxin activity, but also for evaluating the characteristics of different types of NTX. The rat CMAP test is straightforward, highly reproducible, and can directly determine the efficacy of toxin preparations through their inhibition of neuromuscular transmission. Thus, this method may be suitable for pharmacology studies and the quality control of toxin preparations. Copyright 2009 Elsevier Ltd. All rights reserved.

[Advantages of combined therapies in cosmetic medicine for the treatment of face aging: botulinum toxin, fillers and mesotherapy].

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Braccini, F; Dohan Ehrenfest, D M

2010-01-01

Non surgical cosmetic medicine procedures for the face are developing considerably, as they deliver good results using simple, non invasive, atraumatic and reproducible techniques. Aesthetic mesotherapy, also known as anti-aging mesotherapy, uses intra-dermal injections of a nutritive and moisturizing solution to improve brightness, skin hydration and tonus, and also smooth out superficial wrinkles. Subcutaneous filler injections enable to fill wrinkles and folds; by using high density products it is also able to provide genuine facial volumetric reconstruction. Finally, botulinum toxin acts by reducing certain muscle contractions to smooth out expression lines and folds induced by facial dynamics. In this article, we explore the concept of combined therapy and describe our experience associating anti-aging mesotherapy (NCTF-135HA, Filorga, Paris, France), hyaluronic acid based fillers (X-HA3 and X-HA-Volume, Filorga, Paris, France) and botulinum toxin (Vistabel, Allergan, Irvine CA, USA). A therapy combining anti-aging mesotherapy, botulinum toxin and filler injections, offers full treatment of the 3 biological levels of the covering tissues. This non-invasive therapeutic strategy brings patient satisfaction through a global approach to facial aging.

Anticholinergic versus botulinum toxin A comparison trial for the treatment of bothersome urge urinary incontinence: ABC trial.

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Visco, Anthony G; Brubaker, Linda; Richter, Holly E; Nygaard, Ingrid; Paraiso, Marie Fidela; Menefee, Shawn A; Schaffer, Joseph; Wei, John; Chai, Toby; Janz, Nancy; Spino, Cathie; Meikle, Susan

2012-01-01

This trial compares the change in urgency urinary incontinence episodes over 6 months, tolerability and cost effectiveness between women receiving daily anticholinergic therapy plus a single intra-detrusor injection of saline versus a single intra-detrusor injection of 100 U of botulinum toxin A plus daily oral placebo tablets. We present the rationale and design of a randomized-controlled trial, Anticholinergic versus Botulinum Toxin, Comparison Trial for the Treatment of Bothersome Urge Urinary Incontinence: ABC trial, conducted by the NICHD-funded Pelvic Floor Disorders Network. We discuss the innovative nature of this trial and the challenges related to choice of patient population, maintaining masking, cost effectiveness, ethical considerations, measuring adherence, and placebo development and testing. Enrollment began in April, 2010. 242 participants will be randomized and primary outcome data analysis is anticipated to begin in mid 2012. Several challenges in the trial design are discussed. Randomization to placebo intra-detrusor injections may limit recruitment, potentially impacting generalizability. Other challenges included the heavy marketing of drugs for overactive bladder which could impact recruitment of drug-naïve women. In addition, anticholinergic medications often cause dry mouth, making masking difficult. Finally, adverse reporting of transient urinary retention is challenging as there is no standardized definition; yet this is the most common adverse event following intra-detrusor botulinum toxin injection. The ABC trial will help women with urgency urinary incontinence balance efficacy, side effects and cost of anticholinergic medication versus botulinum toxin intra-detrusor injection. The results have the potential to fundamentally change the therapeutic approach to this condition. Copyright © 2011 Elsevier Inc. All rights reserved.

Botulinum toxin: An emerging therapy in female bladder outlet obstruction

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Aditya A Pradhan

2009-01-01

Discussion: There is a gradual improvement in symptoms over time and the maximal effect occurred at 10-14 days. The duration of improvement was approximately 16.8 weeks. All patients were satisfied by the degree of improvement felt. Conclusions: Botulinum toxin proved successful in improving the voiding characteristics. It possibly acts at the zone of hypertonicity at the bladder neck or midurethra. The only disadvantage is the high cost of the drug.

Sustained improvement of reading symptoms following botulinum toxin A injection for convergence insufficiency

DEFF Research Database (Denmark)

Saunte, Jon Peiter; Holmes, Jonathan M

2014-01-01

.008) at near, although 2 patients had a temporary intermittent esotropia in the distance with diplopia associated with difficulty driving. At 6 months, when the pharmacological effect of botulinum toxin had completely worn off, patients still maintained a small reduction of exodeviation (median 4 PD, p=0...

Long-Term Resolution of Severe Ankle Contractures Using Botulinum Toxin, Serial Casting, Splinting, and Motor Retraining.

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Leung, Joan; Stroud, Katarina

2018-01-01

Purpose: Serial casting for ankle contractures is traditionally performed in prone, a position that patients may not easily tolerate. Also, although serial casting is effective in correcting contracture, its effect dissipates quickly. This case report describes a procedure for performing casting for ankle contractures in a supine or sitting position. It also describes a process that enables the effect of serial casting to be maintained long term. Client Description: The client was an adult who had suffered traumatic brain injury and severe bilateral ankle contractures. Intervention: He received botulinum toxin and serial casting for his bilateral ankle contractures, one ankle at 8 months and the other at 13 months after the injury. He then underwent a programme of splinting and motor training. Measures and Outcome: The client gained more than 40° dorsiflexion for both ankles after receiving botulinum toxin injections and serial casting. The improvement in ankle range enabled him to progress to walking practice. Ankle splinting was gradually reduced. On discharge at 25 months post-injury, the ankle joint range was maintained. Implications: The use of botulinum toxin and serial casting, followed by an intensive programme of splinting and motor training, may be an option to consider for effective long-term resolution of severe contractures after acquired brain injury.

The Role of Botulinum Toxin Type A in the Clinical Management of Refractory Anterior Knee Pain

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Barbara J. Singer

2015-08-01

Full Text Available Anterior knee pain is a highly prevalent condition affecting largely young to middle aged adults. Symptoms can recur in more than two thirds of cases, often resulting in activity limitation and reduced participation in employment and recreational pursuits. Persistent anterior knee pain is difficult to treat and many individuals eventually consider a surgical intervention. Evidence for long term benefit of most conservative treatments or surgical approaches is currently lacking. Injection of Botulinum toxin type A to the distal region of vastus lateralis muscle causes a short term functional “denervation” which moderates the influence of vastus lateralis muscle on the knee extensor mechanism and increases the relative contribution of the vastus medialis muscle. Initial data suggest that, compared with other interventions for anterior knee pain, Botulinum toxin type A injection, in combination with an active exercise programme, can lead to sustained relief of symptoms, reduced health care utilisation and increased activity participation. The procedure is less invasive than surgical intervention, relatively easy to perform, and is time- and cost-effective. Further studies, including larger randomized placebo-controlled trials, are required to confirm the effectiveness of Botulinum toxin type A injection for anterior knee pain and to elaborate the possible mechanisms underpinning pain and symptom relief.

Treating glabellar lines with botulinum toxin type A-hemagglutinin complex: A review of the science, the clinical data, and patient satisfaction

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Koenraad De Boulle

2010-04-01

Full Text Available Koenraad De Boulle1, Steven Fagien2, Boris Sommer3, Richard Glogau41Aalst Dermatology Clinic, Aalst, Belgium; 2Aesthetic Eyelid Plastic, Surgery, Boca Raton, FL, USA; 3Aesthetic Dermatology, Frankfurt, Germany; 4University of California, San Francisco, USAAbstract: Botulinum toxin type A treatment is the foundation of minimally invasive aesthetic facial procedures. Clinicians and their patients recognize the important role, both negative and positive, that facial expression, particularly the glabellar frown lines, plays in self-perception, emotional well-being, and perception by others. This article provides up-to-date information on fundamental properties and mechanisms of action of the major approved formulations of botulinum toxin type A, summarizes recent changes in naming conventions (nonproprietary names mandated by the United States Food and Drug Administration, and describes the reasons for these changes. The request for these changes provides recognition that formulations of botulinum toxins (eg, onabotulinumtoxinA and abobotulinumtoxinA are not interchangeable and that dosing recommendations cannot be based on any one single conversion ratio. The extensive safety, tolerability, and efficacy data are summarized in detail, including the patient-reported outcomes that contribute to overall patient satisfaction and probability treatment continuation. Based on this in-depth review, the authors conclude that botulinum toxin type A treatment remains a cornerstone of facial aesthetic treatments, and clinicians must realize that techniques and dosing from one formulation cannot be applied to others, that each patient should undergo a full aesthetic evaluation, and that products and procedures must be selected in the context of individual needs and goals.Keywords: onabotulinumtoxinA, botulinum toxin type A, cosmetic, glabellar, patient satisfaction

Detection and Quantification of Biologically Active Botulinum Neurotoxin Serotypes A and B Using a Förster Resonance Energy Transfer-Based Quantum Dot Nanobiosensor

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Wang, Yun [Center for Food; Fry, H. Christopher [Center for Nanoscale Materials, Argonne National Laboratory, 9700 S. Cass Avenue, Lemont, DuPage County, Illinois 60439, United States; Skinner, Guy E. [Center for Food; Schill, Kristin M. [Center for Food; Duncan, Timothy V. [Center for Food

2017-03-20

Botulinum neurotoxin (BoNT) is the most potent toxin known. The ingestion of food contaminated with biologically active BoNT causes foodborne botulism, which can lead to respiratory paralysis, coma, and death after ingestion of as little as 70 mu g for a 70 kg human. Because of its lethality and challenges associated with current detection methods, there is an urgent need for highly sensitive rapid screening techniques capable of detecting biologically active BoNT. Here, we describe a Forster resonance energy transfer-based nanobiosensor that uses quantum dots (QDs) and two specific quencher-labeled peptide probes to detect and differentiate two biologically active forms of BoNT, serotypes A and B, which were responsible for 80% of human foodborne botulism cases in the U.S. from 2012 to 2015. Each peptide probe contains an enzymatic cleavage site specific to only one serotype. QDs were selected based on the spectral overlap with the quenchers. In the presence of the target BoNT serotype, the peptide probe is cleaved and the quenching of QD photoluminescence (PL) is reduced, giving a signal that is easily detected by a PL spectrophotometer. This sensor performance was evaluated with light chains of BoNT/A and BoNT/B (LcA and LcB), catalytic domains of the respective serotypes. LcA and LcB were detected in 3 h with limits of detection of 0.2 and 2 ng/mL, respectively. The specificity of the sensor was evaluated, and no cross-reactivity from nontarget serotypes was observed with 2 h of incubation. Because each serotype-specific peptide is conjugated to a QD with a unique emission wavelength, multiple biologically active BoNT serotypes could be detected in one PL spectrum. The sensor was also shown to be responsive to BoNT/A and BoNT/B holotoxins. Good performance of this sensor implies its potential application as a rapid screening method for biologically active BoNT/A and BoNT/B in the laboratory and in the field.

Computer-Aided Design/Computer-Assisted Manufacture-Derived Needle Guide for Injection of Botulinum Toxin into the Lateral Pterygoid Muscle in Patients with Oromandibular Dystonia.

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Yoshida, Kazuya

2018-01-01

To evaluate the effectiveness and safety of botulinum toxin administration into the inferior head of the lateral pterygoid muscle of patients with jaw opening dystonia by using a computer-aided design/computer-assisted manufacture (CAD/CAM)-derived needle guide. A total of 17 patients with jaw opening dystonia were enrolled. After the patient's computed tomography (CT) scan was imported and fused with a scan of a plaster cast model of the maxilla, the optimal needle insertion site over the lateral pterygoid muscle was determined using the NobelClinician software. A total of 13 patients were injected both with and without the guide, and 4 patients underwent guided injection alone. The therapeutic effects of botulinum toxin injection and its associated complications were statistically compared between the guided and unguided procedures using paired t test. Botulinum toxin therapy was performed 42 and 32 times with and without the guides, respectively. The needle was easily inserted without any complications in all procedures. There was a significant difference (P < .001) between the mean comprehensive improvements observed with (66.3%) and without (54.4%) the guides. The findings suggest that the use of needle guides during the injection of botulinum toxin into the inferior head of the lateral pterygoid muscle is very useful for aiding the accurate and safe administration of botulinum toxin therapy for jaw opening dystonia.

Investigation of inactivation of Clostridium botulinum toxin by nuclear radiation. Final report. Untersuchung zur Desaktivierung des Clostridium botulinum Toxins durch Kernstrahlung. Endbericht

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Kaltenhaeuser, A.; Werner, K.H.

1989-01-01

The effect of nuclear radiation on the toxicity and the molecular structure of the toxin produced by the microorganism Clostridium botulinum type A was investigated. The radiation induced changes in the structure of the toxin molecule. This effect is influenced by the composition or the medium above the toxin solution as well as by the temperature during the irradiation. The results of the investigation indicate that with increasing irradiation dose a new molecule was formed with immunological properties similar to the properties of the original molecule however with a greater molecular weight. After exposure to a radiation dose of 3,4 Mrad at normal temperature in air, complete detoxification of the substance was found. Immunizing experiments with the toxoid with two guinea-pigs indicated a pronounced increase of the antibody titer in the serum after 4 weeks. Vaccination experiments with the toxoid on animals show, that the protection against the effect of the toxin corresponds to the demands of the European Pharmacopoeia. The efficiency of the toxoid shows a similar efficiency as toxoids produced by chemical methods. The production of a toxoid-viccine with the relatively simple method of nuclear radiation appears possible. (orig./MG) With 12 refs., 3 tabs., 11 figs.

The first non Clostridial botulinum-like toxin cleaves VAMP within the juxtamembrane domain.

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Zornetta, Irene; Azarnia Tehran, Domenico; Arrigoni, Giorgio; Anniballi, Fabrizio; Bano, Luca; Leka, Oneda; Zanotti, Giuseppe; Binz, Thomas; Montecucco, Cesare

2016-07-22

The genome of Weissella oryzae SG25T was recently sequenced and a botulinum neurotoxin (BoNT) like gene was identified by bioinformatics methods. The typical three-domains organization of BoNTs with a N-terminal metalloprotease domain, a translocation and a cell binding domains could be identified. The BoNT family of neurotoxins is rapidly growing, but this was the first indication of the possible expression of a BoNT toxin outside the Clostridium genus. We performed molecular modeling and dynamics simulations showing that the 50 kDa N-terminal domain folds very similarly to the metalloprotease domain of BoNT/B, whilst the binding part is different. However, neither the recombinant metalloprotease nor the binding domains showed cross-reactivity with the standard antisera that define the seven serotypes of BoNTs. We found that the purified Weissella metalloprotease cleaves VAMP at a single site untouched by the other VAMP-specific BoNTs. This site is a unique Trp-Trp peptide bond located within the juxtamembrane segment of VAMP which is essential for neurotransmitter release. Therefore, the present study identifies the first non-Clostridial BoNT-like metalloprotease that cleaves VAMP at a novel and relevant site and we propose to label it BoNT/Wo.

Botulinum toxin for treating unilateral apraxia of eyelid opening in a patient with congenital myotonia

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Estrella Fernández

Full Text Available ABSTRACT A 37-year-old female presented with severe apraxia of lid opening (ALO affecting the right upper lid associated with Becker congenital myotonia (MC. The patient had a history of right upper lid ptosis for 25 years that was exacerbated over the previous month with severe incapacity to open her right eye. No other associated neurological or ophthalmic symptoms were observed. The patient was treated with botulinum toxin (BoNT-A injection into the pretarsal and lateral canthus region of the orbicularis oculi of the affected eyelid. Treatment with BoNT-A is an effective method of managing ALO in Becker MC. This is the first case of unilateral ALO in the course of Becker MC that was successfully treated with injections of botulinum toxin.

Efficacy of Repeated Botulinum Toxin Type A Injections for Spastic Equinus in Children with Cerebral Palsy-A Secondary Analysis of the Randomized Clinical Trial.

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Hong, Bo Young; Chang, Hyun Jung; Lee, Sang-Jee; Lee, Soyoung; Park, Joo Hyun; Kwon, Jeong-Yi

2017-08-21

Botulinum toxin A is considered an important tool to control spasticity in children with cerebral palsy. Several factors are known to affect the efficacy of botulinum toxin, such as dosage, appropriate muscle selection and application, age, and accompanying therapy. A multicenter, double-blind, randomized, prospective phase III clinical trial of botulinum toxin A for the treatment of dynamic equinus in 144 children with cerebral palsy was performed to compare the efficacies of letibotulinumtoxin A and onabotulinumtoxin A. Secondary analyses were performed to evaluate factors that affected the outcome, focusing on the number of times injections were repeated. Effectiveness was defined as a change of 2 or more in the physician's rating scale. Multivariate regression analyses were performed with multiple variables. The first injection of botulinum toxin A significantly improved D subscale of Gross Motor Function Measure-88 scores at 3 months compared to repeated injections ( p < 0.05). After 6 months, patients who had one injection or none before the study showed significantly better outcomes than those who had more than one injection in terms of observational gait scores.

Yesterday and Today: The Impact of Research Conducted at Camp Detrick on Botulinum Toxin.

Science.gov (United States)

Lebeda, Frank J; Adler, Michael; Dembek, Zygmunt F

2018-05-01

This review summarizes the research conducted on botulinum toxin (BoTx) from 1943 to 1956 by a small group of Camp Detrick investigators and their staff. A systematic, cross-disciplinary approach was used to develop effective vaccines against this biological warfare threat agent. In response to the potential need for medical countermeasures against BoTx during World War II, the refinement of isolation and purification techniques for BoTx successfully led to the large-scale production of botulinum toxoid vaccines. In addition, the work at Camp Detrick provided the foundation for the subsequent use of BoTx as a tool for studying the trophic regulation of skeletal muscle within motor neuron terminals and, more recently, for elucidation of the intricate details of neurotransmitter release at the molecular level. Indirectly, Camp Detrick investigators also played a significant role in studies that culminated in the use of BoTx as a pharmaceutical product that has been approved by the U.S. Food and Drug Administration for treating movement disorders, autonomic dysfunctions, and other conditions. Online literature searches were performed with Google, Google Scholar, PubMed, the bibliography from the Camp Detrick technical library, and at the Defense Technical Information Center. Reference lists in some of the primary research publications and reviews also provided source material. Search terms included botulinum, botulinus, and Camp Detrick. References related to the subsequent impacts of the Camp Detrick results were selected and cited from reviews and primary references in the more recent literature. Notes on toxin nomenclature and potential sources of error in this study are presented. The literature searches returned 27 citations of Camp Detrick authors, 24 of which were articles in peer-reviewed journals. The publications by these investigators included several disciplines such as biochemistry, immunology, pharmacology, physiology, and toxicology. A fundamental

Use of Botulinum toxin in 55 children with cerebral palsy

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Mohammadi M

2000-10-01

Full Text Available Botulinum toxin A (BTA inhibits presynaptic release of acetylcholine at the neuromuscular junction and has reportedly been successful in the treatment of spastic disorders.To evaluate the effect of botulinum toxin on cerebral palsied children with spastic or mixed type of the disease, especially those patiens having spasticity as a cardinal symptom without joint contracture, we designed the following study. Ninety-one cases (55 of referred patients to pediatic Neurology outpatient clinics of children’s Medical Center were given BTA injections in affected muscles of the lower limb. They were reevaluating 3 to 5 weeks and 3 months later for type of walking and range of affected joints’ movement. The study showed a clinically significant gait improvement in 71.2% of patients (P<0.0005 and also an overall increased range of motion in affected limbs after BTA injection (P<0.04. Side effects occurred only in two cases as transient generalized weakness, gent recurvatum and ptosis. Drug effectiveness was time-limited, lasting abot 3 months in all patients ( a golden time for rehabilitation therapists to improve the patients’ condition. Overall, BTA has improved both the type of walking as well as the range of joints motion in our patients. So its’ administration is suggested in cerebral palsied children if the spasticity is a major and disabling sign

Use of botulinum toxin-A for musculoskeletal pain in patients with whiplash associated disorders [ISRCTN68653575

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Juan Francisco J

2004-02-01

Full Text Available Abstract Background Whiplash associated disorder is commonly linked to motor vehicle accidents and sports injuries. Cervical injury is attributed to rapid extension followed by neck flexion. The exact pathophysiology of whiplash is uncertain but probably involves some degree of aberrant muscle spasms and may produce a wide range of symptoms. The most commonly prescribed pharmacological agents for initial treatment of whiplash-associated pain are oral muscle relaxants and nonsteroidal anti-inflammatory drugs. However, potential systemic adverse effects limit these agents. Physical interventions such as mobilization, manipulation, and exercises have proved beneficial for pain and dysfunction but only on a time-limited basis. Little evidence suggests that physical therapy specifically aimed at the musculature (e.g., transcutaneous electrical nerve stimulation, ultrasonography, heat, ice, and acupuncture improves prognosis in acute whiplash associated disorder. A new approach to treatment is the use of botulinum toxin, which acts to reduce muscle spasms. Methods/design This is a prospective, randomized, controlled clinical trial and botulinum toxin-A (Botox® injections will be compared with placebo injections. The primary objective is to determine the efficacy of Botox® in the management of musculoskeletal pain in whiplash associated disorders. Discussion Botulinum toxin type-A toxin has been studied in small trials on whiplash associated disorder patients and has generally been found to relieve pain and improve range of motion. Specifically, we seek to assess the efficacy of Botox® in reducing pain and to improve the cervical spine range of movement, during the 6-month trial period.

Dynamic Model of Applied Facial Anatomy with Emphasis on Teaching of Botulinum Toxin A

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Ricardo Frota Boggio, MD, PhD

2017-11-01

Conclusion:. By making it possible to interrelate anatomy of a function, body painting is proposed in the present study as an innovative method, which in a demonstrative and highly didactic manner presents great potential as a teaching tool in the application of botulinum toxin A.

Clinical Study of New Tetravalent (Type A, B, E, and F) Botulinum Toxoid Vaccine Derived from M Toxin in Japan.

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Torii, Yasushi; Sugimoto, Nakaba; Kohda, Tomoko; Kozaki, Shunji; Morokuma, Kazunori; Horikawa, Yoshikane; Ginnaga, Akihiro; Yamamoto, Akihiko; Takahashi, Motohide

2017-07-24

Botulinum toxin is the most poisonous substance known, and is believed to be a highly lethal as a biological weapon; researchers of the toxin are exposed to this hazard. Botulinum toxoid vaccines have been produced and used in Japan. However, since clinical studies involving these vaccines were conducted before establishment of the Ethical Guidelines for Clinical Research in Japan, their immunogenicity and safety were not systematically assessed. In this study, we produced a new tetravalent (type A, B, E, and F) botulinum toxoid vaccine, the first ever to be derived from M toxin, and conducted quality control tests with reference to the Minimum Requirements in Japan for adsorbed tetanus toxoid vaccine. Subsequently, a clinical study using the new vaccine in 48 healthy adult volunteers was conducted according to the guidelines in Japan. No clinically serious adverse event was noted. Neutralizing antibody titers for each type of toxin in the participants' sera, 1 month after the 4th injection were more than 0.25 IU/mL, indicating sufficient protection. This study demonstrated that the vaccine has marked immunogenicity and is safe for use in humans.

Evaluating the functional outcomes of ultrasound-guided botulinum toxin type A injections using the Euro-musculus approach for upper limb spasticity treatment in post-stroke patients; an observational study.

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Buyukavci, Raikan; Akturk, Semra; Ersoy, Yüksel

2018-02-07

Ultrasound-guided botulinum toxin type A injection is an effective treatment for spasticity. Euro-musculus spasticity approach is a new method for administering injections to the correct point of the correct muscle. The clinical outcomes of this practical approach is not yet available in the literature. The purpose of this study was to evaluate the effects on spasticity and the functional outcomes of ultrasound guided botulinum toxin type A injections via the Euro-musculus spasticity approach to treat upper limb spasticity in post-stroke patients. An observational study. Inpatient post-stroke patients. Twenty five post-stroke patients with post-stroke upper limb spasticity were recruited. The ultrasound-guided botulinum toxin type A injections were administered into the spastic target muscles using the Euro-musculus spasticity approach, and all of the patients were enrolled in rehabilitation programmes after the injections. This research included the innervation zone and injection site figures and ultrasound images of each muscle in the upper limb. The degree of spasticity was assessed via the Modified Ashworth Scale and the upper limb motor function via the Fugl Meyer Upper Extremity Scale at the baseline and 4 and 12 weeks after the botulinum toxin type A injection. Significant decreases in the Modified Ashworth Scale scores of the upper limb flexor muscle tone measured 4 and 12 weeks after the botulinum toxin type A injection were found when compared to the baseline scores (pbotulinum toxin type A injection via the Euro- musculus spasticity approach is a practical and effective method for administering injections to the correct point of the correct muscle. Ultrasound-guided botulinum toxin type A injections combined with rehabilitation programmes decrease spasticity and improve the upper extremity motor functions in stroke patients. This new approach for ultrasound- guided botulinum toxin type A injection is very practical and effective method for upper

Treating glabellar lines with botulinum toxin type A-hemagglutinin complex: a review of the science, the clinical data, and patient satisfaction.

Science.gov (United States)

De Boulle, Koenraad; Fagien, Steven; Sommer, Boris; Glogau, Richard

2010-04-26

Botulinum toxin type A treatment is the foundation of minimally invasive aesthetic facial procedures. Clinicians and their patients recognize the important role, both negative and positive, that facial expression, particularly the glabellar frown lines, plays in self-perception, emotional well-being, and perception by others. This article provides up-to-date information on fundamental properties and mechanisms of action of the major approved formulations of botulinum toxin type A, summarizes recent changes in naming conventions (nonproprietary names) mandated by the United States Food and Drug Administration, and describes the reasons for these changes. The request for these changes provides recognition that formulations of botulinum toxins (eg, onabotulinumtoxinA and abobotulinumtoxinA) are not interchangeable and that dosing recommendations cannot be based on any one single conversion ratio. The extensive safety, tolerability, and efficacy data are summarized in detail, including the patient-reported outcomes that contribute to overall patient satisfaction and probability treatment continuation. Based on this in-depth review, the authors conclude that botulinum toxin type A treatment remains a cornerstone of facial aesthetic treatments, and clinicians must realize that techniques and dosing from one formulation cannot be applied to others, that each patient should undergo a full aesthetic evaluation, and that products and procedures must be selected in the context of individual needs and goals.

Growth of and toxin production by nonproteolytic Clostridium botulinum in cooked puréed vegetables at refrigeration temperatures.

Science.gov (United States)

Carlin, F; Peck, M W

1996-01-01

Seven strains of nonproteolytic Clostridium botulinum (types B, E, and F) were each inoculated into a range of anaerobic cooked puréed vegetables. After incubation at 10 degrees C for 15 to 60 days, all seven strains formed toxin in mushrooms, five did so in broccoli, four did so in cauliflower, three did so in asparagus, and one did so in kale. Growth kinetics of nonproteolytic C. botulinum type B in cooked mushrooms, cauliflower, and potatoes were determined at 16, 10, 8, and 5 degrees C. Growth and toxin production occurred in cooked cauliflower and mushrooms at all temperatures and in potatoes at 16 and 8 degrees C. The C. botulinum neurotoxin was detected within 3 to 5 days at 16 degrees C, 11 to 13 days at 10 degrees C, 10 to 34 days at 8 degrees C, and 17 to 20 days at 5 degrees C. PMID:8702303

Botulinum toxin to improve results in cleft lip repair: a double-blinded, randomized, vehicle-controlled clinical trial.

Directory of Open Access Journals (Sweden)

Chun-Shin Chang

Full Text Available Most patients with facial scarring would value even a slight improvement in scar quality. Botulinum toxin A is widely used to alleviate facial dynamic rhytides but is also believed to improve scar quality by reducing wound tension during healing. The main objective was to assess the effect of Botulinum toxin on scars resultant from standardized upper lip wounds.In this double-blinded, randomized, vehicle-controlled, prospective clinical trial, 60 consecutive consenting adults undergoing cleft lip scar revision (CLSR surgery between July 2010 and March 2012 were randomized to receive botulinum toxin A (n = 30 or vehicle (normal saline; n = 30 injections into the subjacent orbicularis oris muscle immediately after wound closure. Scars were independently assessed at 6-months follow-up in blinded fashion using: Vancouver Scar Scale (VSS, Visual Analogue Scale (VAS and photographic plus ultrasound measurements of scar widths.58 patients completed the trial. All scar assessment modalities revealed statistically significantly better scars in the experimental than the vehicle-control group.Quality of surgical upper lip scars, which are oriented perpendicular to the direction of pull of the underlying orbicularis oris muscle, is significantly improved by its temporary paralysis during wound healing.ClinicalTrials.gov NCT01429402.

Botulinum toxin-induced acute anterior uveitis in a patient with Behçet's disease under infliximab treatment: a case report.

Science.gov (United States)

Sasajima, Hirofumi; Yagi, Syunsuke; Osada, Hiromu; Zako, Masahiro

2017-05-04

Injections of lipopolysaccharide in animal models generate acute anterior uveitis (also known as endotoxin-induced uveitis), but the effects of lipopolysaccharide injection are unknown in humans. We describe an unusual case in which acute anterior uveitis was dramatically activated subsequent to botulinum toxin injection in a patient with Behçet's disease but the acute anterior uveitis was satisfactorily attenuated by infliximab. A 53-year-old Japanese man had normal ocular findings at his regularly scheduled appointment. He had been diagnosed as having incomplete-type Behçet's disease 11 years before. Three years after the diagnosis he was given systemic infusions of 5 mg/kg infliximab every 8 weeks and he had not experienced a uveitis attack for 8 years with no treatment other than infliximab. Two days after the eye examination, he received intracutaneous botulinum toxin injections to treat axillary hyperhidrosis on both sides. Three hours after the injections, he noted rapidly increasing floaters in his right eye. Four days after the injections, his right eye showed severe acute anterior uveitis with deteriorated aqueous flare and anterior vitreous opacity. He received his scheduled infliximab injection, and the right acute anterior uveitis immediately attenuated. Botulinum toxin may have clinical effects similar to those of lipopolysaccharide in endotoxin-induced uveitis models. To the best of our knowledge, this is the first report to suggest that botulinum toxin may trigger acute anterior uveitis, although the precise mechanism is still unclear.

Botulinum toxin A injection for chronic anal fissures and anal sphincter spasm improves quality of life in recessive dystrophic epidermolysis bullosa

Directory of Open Access Journals (Sweden)

Cassandra Chaptini, MBBS

2015-12-01

Full Text Available We report a 20-year-old female with generalized, severe, recessive dystrophic epidermolysis bullosa who developed secondary chronic anal fissures. This resulted in anal sphincter spasm and severe, disabling pain. She was treated with five botulinum toxin A injections into the internal anal sphincter over a period of 2 years and gained marked improvement in her symptoms. This case demonstrates the successful use of botulinum toxin A injections to relieve anal sphincter spasm and fissuring, with long-term improvement.

Sensory integration in writer's cramp: comparison with controls and evaluation of botulinum toxin effect

NARCIS (Netherlands)

Contarino, M. F.; Kruisdijk, J. J. M.; Koster, L.; Ongerboer de Visser, B. W.; Speelman, J. D.; Koelman, J. H. T. M.

2007-01-01

OBJECTIVE: Abnormal temporal and spatial sensory integration have been described in mixed groups of dystonic patients. We tested somatosensory integration and the effect of botulinum toxin (BoNT) in patients with writer's cramp (WC). METHODS: Median and ulnar SEPs were recorded in 29 WC patients and

Critical analysis of the use of onabotulinumtoxinA (botulinum toxin type A in migraine

Directory of Open Access Journals (Sweden)

Robertson CE

2012-01-01

Full Text Available Carrie E Robertson, Ivan GarzaDepartment of Neurology, Mayo Clinic, Rochester, MN, USAAbstract: OnabotulinumtoxinA, a neurotoxin, has been studied in numerous trials as a novel preventive therapy for migraine headache. The data would support that it may be effective at reducing headache days in patients suffering from chronic migraine (≥15 headache days/month, with eight or more of those migraine headache days. The mechanism by which onabotulinumtoxinA exerts its effects on migraine is not yet understood. It is known to inhibit acetylcholine release at the neuromuscular junction, but this probably does not explain the observed antinociceptive properties noted in preclinical and clinical trials. This review will discuss the known mechanisms of action of botulinum toxin type A, and will review the available randomized, placebo-controlled trials that have looked at its efficacy as a migraine preventative. We also describe the onabotulinumtoxinA injection sites used at our institution.Keywords: botulinum toxin, prophylaxis, onabotulinumtoxinA, mechanism, migraine, prevention

The Structure of the Neurotoxin- Associated Protein HA33/A from Clostridium botulinum Suggests a Reoccurring Beta-Trefoil Fold in the Progenitor Toxin Complex

National Research Council Canada - National Science Library

Arndt, Joseph W; Gu, Jenny; Jaroszewski, Lukasz; Schwarzenbacher, Robert; Hanson, Michael A; Lebeda, Frank L; Stevens, Raymond C

2004-01-01

The hemagglutinating protein HA33 from Clostridium botulinum is associated with the large botulinum neurotoxin secreted complexes and is critical in toxin protection, internalization, and possibly activation...

Neurorehabilitation with versus without resistance training after botulinum toxin treatment in children with cerebral palsy

DEFF Research Database (Denmark)

Bandholm, Thomas Quaade; Jensen, Bente Rona; Nielsen, Lone M

2012-01-01

Objective: To compare the effects of physical rehabilitation with (PRT) and without (CON) progressive resistance training following treatment of spastic plantarflexors with botulinum toxin type A (BoNT) in children with cerebral palsy (CP). Methods: Fourteen children with CP performed supervised...

Case Report: Impact of Botulinum Toxin Injection on Function of Affected Upper Extremity in A Patient, 16 Years after Stroke

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Malek Amini

2012-10-01

Full Text Available Objective: Case report Impact of Botulinum Toxin injection on function of affected upper extremity in a patient after 16 years since stroke (CVA. Botulinum toxin injection is one the treatments in spasticity reduction and consequently in recovery of upper limb function in stroke patients. The purpose of this case study is to report the effect of Botulinum toxin injection on upper extremity function after 16 years of stroke. Materials & Methods: The patient was a 63-year-old man who has had a cerebrovascular accident that happened in the left hemisphere about 16 years ago, and as a result, a paresis in dominant hand and arm. Although the patient was able to perform simple movements but he was complaining about the slowness and stiffness in the movements. To treat spasticity the Botulinum toxin type A was used. Injection into selected muscles of hemiparetic upper limb was done by a specialist physician and was between 50-150IU based on specific volume of each muscle. After injection, the patient was monitored for 3 months and at the end of each month, the assessments were reevaluated. During this period, although research team suggested the patient to continue the rehabilitation but for personal reasons he didn’t participate in any treatment and didn`t receive any other antispasmodic medications. Results: An increase in range of motion was seen in all joints but this improvement was not significant. The greatest improvement in passive and active range of motion was seen in Metacarpophalengeal joints. At the end of each month, compared to the first month the recovery of function in upper extremity was significant. Maximum recovery of upper extremity function was related to the hand section of fugl-meyer assessment. At the end of the first month, spasticity significantly decreased so that the patient was able to extend all his joints more easily than before injection. Although spasticity never reached zero. Conclusion: Botulinum toxin injection

Botulinum Toxin for the Management of Sjögren Syndrome-Associated Recurrent Parotitis.

Science.gov (United States)

O'Neil, Luke M; Palme, Carsten E; Riffat, Faruque; Mahant, Neil

2016-12-01

Recurrent parotitis is a rare manifestation of Sjögren syndrome. The management of recurrent parotitis is challenging because conservative methods may be of limited efficacy and invasive approaches carry the risk of complications. Botulinum toxin has been shown to reduce salivary flow, and consequently, the results of its use in the management of recurrent parotitis have been encouraging. A 65-year-old female patient with recurrent parotitis due to Sjögren syndrome was referred to us, complaining of weekly bouts of inflammation. She required a course of antibiotics monthly to control bacterial superinfections. We treated her with onabotulinumtoxinA injections into both parotid glands at regular intervals. After her second injection cycle, she denied further inflammatory bouts, has not required antibiotics in more than 36 months, and denied any side effects. Botulinum toxin may be a safe and effective method of treating Sjögren syndrome-associated recurrent parotitis. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Botulinum Toxin as an Alternative to Treat the Spasm of the Near Reflex.

Science.gov (United States)

Laria, Carlos; Merino-Suárez, María L; Piñero, David P; Gómez-Hurtado, Arantxa; Pérez-Cambrodí, Rafael J

2015-01-01

We describe the case of an eight-year-old girl with complaints of headaches and blurred vision (uncorrected visual acuity: 0.1 decimal) that showed on examination miotic pupils, pseudomyopia, no ocular motility restrictions, and no associated neurological disease. After initial treatment with cyclopentolate for two months, pseudomyopia persisted with an intermittent and variable esotropia. Spectacles of +1 both eyes and atropine 1% one drop daily were then prescribed. The situation improved and remained stable for several weeks, with pseudomyopia and esotropia reappearing later. Finally, botulinum toxin (2.5 iu Botox) was injected in the medial rectus muscle on two occasions and a visual therapy program based on the stimulation of fusional divergence, diplopia, and stereopsis consciousness was recommended. This prescription was combined with the use of atropine during the first few weeks. Orthotropia and corrected distance visual acuity of 1.0 were found three months after treatment. The evolution and clinical results of this case report suggest that botulinum toxin in combination with other therapeutic alternatives may be useful in the treatment of spasm of the near reflex.

Towards New Uses of Botulinum Toxin as a Novel Therapeutic Tool

OpenAIRE

Pickett, Andy; Perrow, Karen

2011-01-01

The uses of botulinum toxin in the fields of neurology, ophthalmology, urology, rehabilitation medicine and aesthetic applications have been revolutionary for the treatment of patients. This non-invasive therapeutic has continually been developed since first discovered in the 1970s as a new approach to what were previously surgical treatments. As these applications develop, so also the molecules are developing into tools with new therapeutic properties in specific clinical areas. This review ...

Botulinum toxin injections for low-back pain and sciatica.

Science.gov (United States)

Waseem, Zeeshan; Boulias, Chris; Gordon, Allan; Ismail, Farooq; Sheean, Geoffrey; Furlan, Andrea D

2011-01-19

Adequate relief from low-back pain (LBP) is not always possible. Emerging evidence suggests a role for botulinum neurotoxin (BoNT) injections in treating pain disorders. Proponents of BoNT suggest its properties can decrease muscle spasms, ischemia and inflammatory markers, thereby reducing pain. To determine the effects of botulinum toxin injections in adults with LBP. We searched CENTRAL (The Cochrane Library 2009, issue 3) and MEDLINE, EMBASE, and CINAHL to August 2009; screened references from included studies; consulted with content experts and Allergan. We included published and unpublished randomised controlled trials without language restrictions We included randomised trials that evaluated BoNT serotypes versus other treatments in patients with non-specific LBP of any duration. Two review authors selected the studies, assessed the risk of bias using the Cochrane Back Review Group criteria, and extracted the data using standardized forms. We performed a qualitative analysis due to lack of data. We excluded evidence from nineteen studies due to non-randomisation, incomplete or unpublished data. We included three randomised trials (N =123 patients). Only one study included patients with chronic non-specific LBP; the other two examined unique subpopulations. Only one of the three trials had a low risk of bias and demonstrated that BoNT injections reduced pain at three and eight weeks and improved function at eight weeks better than saline injections. The second trial showed that BoNT injections were better than injections of corticosteroid plus lidocaine or placebo in patients with sciatica attributed to piriformis syndrome. The third trial concluded that BoNT injections were better than traditional acupuncture in patients with third lumbar transverse process syndrome. Both studies with high risk of bias had several key limitations. Heterogeneity of the studies prevented meta-analysis. There is low quality evidence that BoNT injections improved pain, function

Long-term effect of botulinum toxin on impairment and functional health in cervical dystonia

NARCIS (Netherlands)

Brans, J. W.; Lindeboom, R.; Aramideh, M.; Speelman, J. D.

1998-01-01

We investigated the long-term effect of botulinum toxin type A (BTA) on impairment as well as functional health in terms of disability, handicap, and quality of life in 64 patients with cervical dystonia. These patients, who first participated in a double-blind trial, were followed for another 12

Multidose Botulinum Toxin A for Intralaryngeal Injection: A Cost Analysis.

Science.gov (United States)

Gilbert, Mark R; Young, VyVy N; Smith, Libby J; Rosen, Clark A

2018-01-04

Botulinum toxin A (BtxA) injection is the mainstay treatment for laryngeal dystonias. BtxA product labeling states that reconstituted toxin should be used within 4 hours on a single patient despite several studies that have demonstrated multidose BtxA to be safe and effective. Many insurance carriers mandate the use of an outside pharmacy which necessitates a single-use approach. This study compares the cost savings of multidose BtxA for laryngeal dystonia compared to single-use. This is a retrospective review and projected cost savings analysis. Records and billing information were reviewed for patients receiving BtxA for intralaryngeal injection at a single laryngology division in 2015. Inclusion criteria included CPT 64617 or J0585; exclusion criteria included CPT 64616. The price of BtxA 100 unit vial for calculation was $670. A total of 142 patients were seen for intralaryngeal BtxA injection resulting in 337 visits over 1 year. The average BtxA dose per visit was 2.86 units with an average of 3.06 procedure visits per year. The calculated cost of BtxA treatment using a single vial approach was found to be $2,050 per patient per year. If billed instead for $7/unit with 5 units wastage charge per visit, the yearly per patient charge is $168. Single vial-use of BtxA injection thus represents a 1,118% price increase versus multidose use. When estimated for yearly prevalence of spasmodic dysphonia, multidose BtxA use would save almost $100 million annually. Multidose botulinum toxin A application utilizing per unit billing is significantly less expensive than per single-use vial billing and would save the health-care system significant amount of money without any sacrifice in safety or effectiveness. Copyright © 2018. Published by Elsevier Inc.

[Definition of botulinum toxin failure in neurogenic detrusor overactivity: Preliminary results of the DETOX survey].

Science.gov (United States)

Peyronnet, B; Sanson, S; Amarenco, G; Castel-Lacanal, E; Chartier-Kastler, E; Charvier, K; Damphousse, M; Denys, P; de Seze, M; Egon, G; Even, A; Forin, V; Karsenty, G; Kerdraon, J; le Normand, L; Loche, C-M; Manunta, A; Mouracade, P; Phe, V; Previnaire, J-G; Ruffion, A; Saussine, C; Schurch, B; Game, X

2015-12-01

There is currently no guideline regarding the management of neurogenic detrusor overactivity (NDO) refractory to intra-detrusor botulinum toxin injections. The primary objective of the present study was to find a consensus definition of failure of botulinum toxin intra-detrusor injections for NDO. The secondary objective was to report current trends in the managment of NDO refractory to botulinum toxin. A survey was created, based on data drawn from current literature, and sent via e-mail to all the experts form the Group for research in neurourology in french language (GENULF) and from the comittee of neurourology of the French urological association (AFU). The experts who did not answer to the first e-mail were contacted again twice. Main results from the survey are presented and expressed as numbers and proportions. Out of the 42 experts contacted, 21 responded to the survey. Nineteen participants considered that the definition of failure should be a combination of clinical and urodynamics criteria. Among the urodynamics criteria, the persistence of a maximum detrusor pressure>40 cm H2O was the most supported by the experts (18/21, 85%). According to the vast majority of participants (19/21, 90.5%), the impact of injections on urinary incontinence should be included in the definition of failure. Regarding the management, most experts considered that the first line treatment in case of failure of a first intra-detrusor injection of Botox(®) 200 U should be a repeat injection of Botox(®) at a higher dosage (300 U) (15/20, 75%), regardless of the presence or not of urodynamics risk factors of upper tract damage (16/20, 80%). This work has provided a first overview of the definition of failure of intra-detrusor injections of botulinum toxin in the management of NDO. For 90.5% of the experts involved, the definition of failure should be clinical and urodynamic and most participants (75%) considered that, in case of failure of a first injection of Botox(®) 200 U

Studies on the irradiation of toxins of Clostridium botulinum and Staphylococcus aureus

International Nuclear Information System (INIS)

Rose, S.A.; Bailey, N.E.; Stringer, M.F.; Modi, N.K.; Tranter, H.S.; Hambleton, P.

1989-01-01

The effects of irradiation of Clostridium botulinum neutotoxin type A (BNTA) and staphylococcal enterotoxin A (SEA) in gelatin phosphate buffer and cooked mince beef slurries were investigated. Estimation of toxins by immunoassays showed that in buffer, toxins were destroyed by irradiation at 8.0 kGy; in mince slurries however, 45% of BTNA and 27-34% of SEA remained after this level of irradiation. At 23.7 kGy, over twice the dose of irradiation proposed for legal acceptance in the UK, 15% of BNTA and 16-26% of SEA still remained. Increasing concentrations of mince conferred increased protection against the effect of irradiation on both toxins. The biological activity of BNTA was more sensitive to irradiation than the immunological activity. Staphylococcal enterotoxin was more resistant to irradiation than BNTA. Irradiation should therefore only be used in conjunction with good manufacturing practices to prevent microbial proliferation and toxin production prior to irradiation. (author)

Studies on the irradiation of toxins of Clostridium botulinum and Staphylococcus aureus

Energy Technology Data Exchange (ETDEWEB)

Rose, S A; Bailey, N E; Stringer, M F [Campden Food and Drink Research Association, Chipping Campden (UK); Modi, N K; Tranter, H S [Porton International plc., London (UK); Hambleton, P [Centre for Applied Microbiological Research, Porton Down (UK)

1988-10-01

The effects of irradiation of Clostridium botulinum neurotoxin type A (BNTA) and staphylococcal enterotoxin A (SEA) in gelatin phosphate buffer and cooked mince beef slurries were investigated. Estimation of toxins by immunoassays showed that in buffer, toxins were destroyed by irradiation at 8.0 kGy; in mince slurries however, 45% of BTNA and 27-34% of SEA remained after this level of irradiation. At 23.7 kGy, over twice the dose of irradiation proposed for legal acceptance in the UK, 15% of BNTA and 16-26% of SEA still remained. Increasing concentrations of mince conferred increased protection against the effect of irradiation on both toxins. The biological activity of BNTA was more sensitive to irradiation than the immunological activity. Staphylococcal enterotoxin was more resistant to irradiation than BNTA. Irradiation should therefore only be used in conjunction with good manufacturing practices to prevent microbial proliferation and toxin production prior to irradiation. (author).

Studies on the irradiation of toxins of Clostridium botulinum and Staphylococcus aureus

International Nuclear Information System (INIS)

Rose, S.A.; Bailey, N.E.; Stringer, M.F.; Modi, N.K.; Tranter, H.S.; Hambleton, P.

1988-01-01

The effects of irradiation of Clostridium botulinum neurotoxin type A (BNTA) and staphylococcal enterotoxin A (SEA) in gelatin phosphate buffer and cooked mince beef slurries were investigated. Estimation of toxins by immunoassays showed that in buffer, toxins were destroyed by irradiation at 8.0 kGy; in mince slurries however, 45% of BTNA and 27-34% of SEA remained after this level of irradiation. At 23.7 kGy, over twice the dose of irradiation proposed for legal acceptance in the UK, 15% of BNTA and 16-26% of SEA still remained. Increasing concentrations of mince conferred increased protection against the effect of irradiation on both toxins. The biological activity of BNTA was more sensitive to irradiation than the immunological activity. Staphylococcal enterotoxin was more resistant to irradiation than BNTA. Irradiation should therefore only be used in conjunction with good manufacturing practices to prevent microbial proliferation and toxin production prior to irradiation. (author)

Studies on the irradiation of toxins of Clostridium botulinum and Staphylococcus aureus

Energy Technology Data Exchange (ETDEWEB)

Rose, S.A.; Bailey, N.E.; Stringer, M.F. (Campden Food and Drink Research Association, Chipping Campden (UK)); Modi, N.K.; Tranter, H.S. (Centre for Applied Micobiological Research, Porton Down, (UK)); Hambleton, P. (Porton International plc, London (UK))

1989-09-01

The effects of irradiation of Clostridium botulinum neutotoxin type A (BNTA) and staphylococcal enterotoxin A (SEA) in gelatin phosphate buffer and cooked mince beef slurries were investigated. Estimation of toxins by immunoassays showed that in buffer, toxins were destroyed by irradiation at 8.0 kGy; in mince slurries however, 45% of BTNA and 27-34% of SEA remained after this level of irradiation. At 23.7 kGy, over twice the dose of irradiation proposed for legal acceptance in the UK, 15% of BNTA and 16-26% of SEA still remained. Increasing concentrations of mince conferred increased protection against the effect of irradiation on both toxins. The biological activity of BNTA was more sensitive to irradiation than the immunological activity. Staphylococcal enterotoxin was more resistant to irradiation than BNTA. Irradiation should therefore only be used in conjunction with good manufacturing practices to prevent microbial proliferation and toxin production prior to irradiation. (author).

Paralysis of the orbicularis muscle of the eye using botulinum toxin type A in the treatment for dry eye.

Science.gov (United States)

Serna-Ojeda, Juan Carlos; Nava-Castaneda, Angel

2017-03-01

To evaluate the efficacy of botulinum toxin type A injection to cause orbicularis eyelid muscle paralysis to improve dry eye signs and symptoms. A prospective, randomized, comparative eye-to-eye and interventional study was performed. Patients with dry eye symptoms and positive fluorescein corneal staining were included. Randomly one eyelid received a subcutaneous injection of botulinum toxin in the medial orbicularis muscle portion of the lower eyelid, and the other eye received placebo. The subjective evaluation was achieved with a questionnaire assessing symptoms, quality of vision and ocular comfort level. The objective evaluation included the measurement of the tear film break-up time (TBUT), Schirmer's test and corneal and conjunctival staining. Twenty patients were included with a mean age of 59.5 years. Two weeks after the botulinum toxin injection, all patients showed a decrease in the horizontal movement of the lower eyelid when blinking. The eyes in the active treatment group showed better scores compared with the sham group in four symptoms 4 weeks after the treatment. The TBUT was higher at 1 and 3 months in the active treatment group. The corneal and conjunctival staining were significantly lower in the active treatment group at 1 and 3 months, and the Schirmer's test showed better measurements in the same group at 2 weeks, 1 month and 3 months. There were no adverse events reported. The injection of botulinum toxin A in the medial part of the lower eyelid is an effective and safe procedure that temporally improves some of the signs and symptoms of patients with dry eye. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Antioxidant effect of minocycline in gingival epithelium induced by Actinobacillus actinomycetemcomitans serotype B toxin

Directory of Open Access Journals (Sweden)

Ernie Maduratna Setiawati

2009-03-01

Full Text Available Background: Actinobacillus actinomycetemcomitans (Aa serotype B has been associated with aggressive periodontitis. Gingival epithelial cell is exquisitely sensitive to the toxin and may lead to the epithel protective barrier disruption. Experimental models show that minocycline is not related to it’s antimicrobial effect and protection against neuron cell apoptosis of a number experimental models of brain injury and Parkinson’s disease. Purpose: This study, examined antioxidant effect of minocycline to inhibit apoptosis of gingival epithelium induced crude toxin bacteria Aa serotype B in mice. Methods: Thirty adult mice strain Swiss Webster (balb C were divided randomly into three groups: control group (group A, toxin group (group B and toxin and minocycline group (group C. The mice were taken at 24 hours after application, and then the tissue sections of gingival epithelium were stained with tunnel assay and immunohistochemistry. Result: Treatment with these toxin induced apoptosis of gingival epithelium and was associated with DNA fragmentation and reduced gluthatione (GSH. Minocycline 100 nM significantly increased GSH and reduced apoptosis (p < 0.05. Minocycline provides antioxidant effect against citotoxicity of bacteria Aa serotipe B. Conclusion: Nanomolar concentration of minocycline potential as new therapeutic agent to prevent progressivity of aggressiveness of periodontitis.

SPASTICITY PATTERNS OF HAND MUSCLES AND BOTULINUM TOXIN THERAPY APPLICATION IN PATIENTS WITH CEREBRAL PALSY WITH UPPER LIMB INVOLVEMENT

Directory of Open Access Journals (Sweden)

O. A. Klochkova

2013-01-01

Full Text Available Botulinum toxin therapy is an effective and safe method of treatment of local spasticity in patients with cerebral palsy (CP. Calculation of botulinum toxin A (BTA dosage based on the spasticity patterns and functional capabilities of the patient proved effective for the hypertonic lower limb muscle spasm treatment and is being applied to BTA injections in hand muscles more often. The article presents contemporary scientific data and results of the original study of BTA injections efficacy for pathologic tension reduction in hand muscles of 52 patients with CP. The authors give detailed description of the upper limb spasticity patterns, their frequency and role in the pathological movement pattern formation. The authors propose BTA dosage calculation for the functional segments of upper limbs, which allows minimizing the total amount of the administered drug and avoiding excessive weakness. The authors have also conducted a follow-up analysis of changes in hand muscle tone for the period of 6 months after the first BTA injection, compared results of botulinum toxin therapy at various clinical forms of CP and given recommendations on the optimum duration of the follow-up period.

Injection of Botulinum Toxin a to Upper Esophageal Sphincter for Oropharyngeal Dysphagia in Two Patients with Inclusion Body Myositis

Directory of Open Access Journals (Sweden)

Louis WC Liu

2004-01-01

Full Text Available Inclusion body myositis (IBM is a progressive degenerative skeletal muscle disease leading to weakening and atrophy of both proximal and distal muscles. Dysphagia is reported in up to 86% of IBM patients. Surgical cricopharyngeal myotomy may be effective for cricopharyngeal dysphagia and there is one published report that botulinum toxin A, injected into the cricopharyngeus muscle using a hypopharyngoscope under general anesthesia, relieved IBM-associated dysphagia. This report presents the first documentation of botulinum toxin A injection into the upper esophageal sphincter using a flexible esophagogastroduodenoscope under conscious sedation, to reduce upper esophageal sphincter pressure and successfully alleviate oropharyngeal dysphagia in two IBM patients.

EGA Protects Mammalian Cells from Clostridium difficile CDT, Clostridium perfringens Iota Toxin and Clostridium botulinum C2 Toxin.

Science.gov (United States)

Schnell, Leonie; Mittler, Ann-Katrin; Sadi, Mirko; Popoff, Michel R; Schwan, Carsten; Aktories, Klaus; Mattarei, Andrea; Azarnia Tehran, Domenico; Montecucco, Cesare; Barth, Holger

2016-04-01

The pathogenic bacteria Clostridium difficile, Clostridium perfringens and Clostridium botulinum produce the binary actin ADP-ribosylating toxins CDT, iota and C2, respectively. These toxins are composed of a transport component (B) and a separate enzyme component (A). When both components assemble on the surface of mammalian target cells, the B components mediate the entry of the A components via endosomes into the cytosol. Here, the A components ADP-ribosylate G-actin, resulting in depolymerization of F-actin, cell-rounding and eventually death. In the present study, we demonstrate that 4-bromobenzaldehyde N-(2,6-dimethylphenyl)semicarbazone (EGA), a compound that protects cells from multiple toxins and viruses, also protects different mammalian epithelial cells from all three binary actin ADP-ribosylating toxins. In contrast, EGA did not inhibit the intoxication of cells with Clostridium difficile toxins A and B, indicating a possible different entry route for this toxin. EGA does not affect either the binding of the C2 toxin to the cells surface or the enzyme activity of the A components of CDT, iota and C2, suggesting that this compound interferes with cellular uptake of the toxins. Moreover, for C2 toxin, we demonstrated that EGA inhibits the pH-dependent transport of the A component across cell membranes. EGA is not cytotoxic, and therefore, we propose it as a lead compound for the development of novel pharmacological inhibitors against clostridial binary actin ADP-ribosylating toxins.

EGA Protects Mammalian Cells from Clostridium difficile CDT, Clostridium perfringens Iota Toxin and Clostridium botulinum C2 Toxin

Science.gov (United States)

Schnell, Leonie; Mittler, Ann-Katrin; Sadi, Mirko; Popoff, Michel R.; Schwan, Carsten; Aktories, Klaus; Mattarei, Andrea; Tehran, Domenico Azarnia; Montecucco, Cesare; Barth, Holger

2016-01-01

The pathogenic bacteria Clostridium difficile, Clostridium perfringens and Clostridium botulinum produce the binary actin ADP-ribosylating toxins CDT, iota and C2, respectively. These toxins are composed of a transport component (B) and a separate enzyme component (A). When both components assemble on the surface of mammalian target cells, the B components mediate the entry of the A components via endosomes into the cytosol. Here, the A components ADP-ribosylate G-actin, resulting in depolymerization of F-actin, cell-rounding and eventually death. In the present study, we demonstrate that 4-bromobenzaldehyde N-(2,6-dimethylphenyl)semicarbazone (EGA), a compound that protects cells from multiple toxins and viruses, also protects different mammalian epithelial cells from all three binary actin ADP-ribosylating toxins. In contrast, EGA did not inhibit the intoxication of cells with Clostridium difficile toxins A and B, indicating a possible different entry route for this toxin. EGA does not affect either the binding of the C2 toxin to the cells surface or the enzyme activity of the A components of CDT, iota and C2, suggesting that this compound interferes with cellular uptake of the toxins. Moreover, for C2 toxin, we demonstrated that EGA inhibits the pH-dependent transport of the A component across cell membranes. EGA is not cytotoxic, and therefore, we propose it as a lead compound for the development of novel pharmacological inhibitors against clostridial binary actin ADP-ribosylating toxins. PMID:27043629

Botulinum toxin type-A injection to treat patients with intractable anismus unresponsive to simple biofeedback training.

Science.gov (United States)

Zhang, Yong; Wang, Zhen-Ning; He, Lei; Gao, Ge; Zhai, Qing; Yin, Zhi-Tao; Zeng, Xian-Dong

2014-09-21

To evaluate the efficacy of botulinum toxin type A injection to the puborectalis and external sphincter muscle in the treatment of patients with anismus unresponsive to simple biofeedback training. This retrospective study included 31 patients suffering from anismus who were unresponsive to simple biofeedback training. Diagnosis was made by anorectal manometry, balloon expulsion test, surface electromyography of the pelvic floor muscle, and defecography. Patients were given botulinum toxin type A (BTX-A) injection and pelvic floor biofeedback training. Follow-up was conducted before the paper was written. Improvement was evaluated using the chronic constipation scoring system. BTX-A injection combined with pelvic floor biofeedback training achieved success in 24 patients, with 23 maintaining persistent satisfaction during a mean period of 8.4 mo. BTX-A injection combined with pelvic floor biofeedback training seems to be successful for intractable anismus.

In Silico Analysis for the Study of Botulinum Toxin Structure

Science.gov (United States)

Suzuki, Tomonori; Miyazaki, Satoru

2010-01-01

Protein-protein interactions play many important roles in biological function. Knowledge of protein-protein complex structure is required for understanding the function. The determination of protein-protein complex structure by experimental studies remains difficult, therefore computational prediction of protein structures by structure modeling and docking studies is valuable method. In addition, MD simulation is also one of the most popular methods for protein structure modeling and characteristics. Here, we attempt to predict protein-protein complex structure and property using some of bioinformatic methods, and we focus botulinum toxin complex as target structure.

Investigation of inactivation of Clostridium botulinum toxin by nuclear radiation

International Nuclear Information System (INIS)

Kaltenhaeuser, A.; Werner, K.H.

1989-01-01

The effect of nuclear radiation on the toxicity and the molecular structure of the toxin produced by the microorganism Clostridium botulinum type A was investigated. The radiation induced changes in the structure of the toxin molecule. This effect is influenced by the composition or the medium above the toxin solution as well as by the temperature during the irradiation. The results of the investigation indicate that with increasing irradiation dose a new molecule was formed with immunological properties similar to the properties of the original molecule however with a greater molecular weight. After exposure to a radiation dose of 3,4 Mrad at normal temperature in air, complete detoxification of the substance was found. Immunizing experiments with the toxoid with two guinea-pigs indicated a pronounced increase of the antibody titer in the serum after 4 weeks. Vaccination experiments with the toxoid on animals show, that the protection against the effect of the toxin corresponds to the demands of the European Pharmacopoeia. The efficiency of the toxoid shows a similar efficiency as toxoids produced by chemical methods. The production of a toxoid-viccine with the relatively simple method of nuclear radiation appears possible. (orig./MG) With 12 refs., 3 tabs., 11 figs [de

The role of kinesiotaping combined with botulinum toxin to reduce plantar flexors spasticity after stroke.

Science.gov (United States)

Karadag-Saygi, Evrim; Cubukcu-Aydoseli, Koza; Kablan, Nilufer; Ofluoglu, Demet

2010-01-01

To evaluate the effect of kinesiotaping as an adjuvant therapy to botulinum toxin A (BTX-A) injection in lower extremity spasticity. This is a single-center, randomized, and double-blind study. Twenty hemiplegic patients with spastic equinus foot were enrolled into the study and randomized into 2 groups. The first group (n=10) received BTX-A injection and kinesiotaping, and the second group (n=10) received BTX-A injection and sham-taping. Clinical assessment was done before injection and at 2 weeks and 1, 3, and 6 months. Outcome measures were modified Ashworth scale (MAS), passive ankle dorsiflexion, gait velocity, and step length. Improvement was recorded in both kinesiotaping and sham groups for all outcome variables. No significant difference was found between groups other than passive range of motion (ROM), which was found to have increased more in the kinesiotaping group at 2 weeks. There is no clear benefit in adjuvant kinesiotaping application with botulinum toxin for correction of spastic equinus in stroke.

Comparison of Pneumatic Dilation with Pneumatic Dilation Plus Botulinum Toxin for Treatment of Achalasia

Directory of Open Access Journals (Sweden)

Alireza Bakhshipour

2010-03-01

Full Text Available Among the therapeutic options for achalasia are pneumatic dilatation (PD, an appropriate long-term therapy, and botulinum toxin injection (BT that is a relatively short-term therapy. This study aimed to compare therapeutic effect of repetitive pneumatic dilation with a combined method (botulinum toxin injection and pneumatic dilation in a group of achalasia patients who are low responder to two initial pneumatic dilations. Thirty- four patients with documented primary achalasia that had low response to two times PD (<50% decrease in symptom score and barium height at 5 minute in timed esophagogram after 3month of late PD were randomized to receive pneumatic dilation (n=18 or botulinum toxin injection and pneumatic dilation by four weeks interval (n=16, PD and BT+PD groups respectively. Symptom scores were evaluated before and at 1, 6 and 12 months after treatment. Clinical remission was defined as a decrease in symptom score ≥ 50% of baseline. There were no significant differences between the two groups in gender, age and achalasia type. Remission rate of patients in BT-PD group in comparison with PD group were 87.5% vs. 67.1% (P = 0.7, 87.5% vs. 61.1% (P = 0.59 and 87.5% vs. 55.5% (P = 0.53 at 1, 6 and 12 months respectively .There were no major complications in either group. The mean symptom score decreased by 62.71% in the BT-PD group (P < 0.002 and 50.77% in the PD group (P < 0.01 at the end of the first year. Despite a better response rate in BT+PD group, a difference was not statistically significant. A difference may be meaningful if a large numbers of patients are included in the study.

An overview of the cosmetic treatment of facial muscles with a new botulinum toxin.

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Wiest, Luitgard G

2009-01-01

Botulinum toxin (BTX) is used nowadays in a much more differentiated way with a much more individualized approach to the cosmetic treatment of patients. To the well known areas of the upper face new indications in the mid and lower face have been added. Microinjection techniques are increasingly used besides the classic intramuscular injection technique. BTX injections of the mid and lower face require small and smallest dosages. The perioral muscles act in concert to achieve the extraordinarily complex movements that control facial expressions, eating, and speech. As the mouth has horizontal as well as vertical movements, paralysis of these perioral muscles has a greater effect on facial function and appearance than does paralysis of muscles of the upper face, which move primarily in vertical direction. It is essential that BTX injections should achieve the desired cosmetic result with the minimum dose without any functional discomfort. In this paper the three-year clinical experience with average dosages for an optimal outcome in the treatment of facial muscles with a newly developed botulinum toxin type A (Xeomin) free from complexing proteins is presented.

Evidence to Use Botulinum Toxin Injections in Tension-Type Headache Management: A Systematic Review.

Science.gov (United States)

Wieckiewicz, Mieszko; Grychowska, Natalia; Zietek, Marek; Wieckiewicz, Gniewko; Smardz, Joanna

2017-11-15

Tension-type headache (TTH) is the most common type of chronic recurring head pain. It can occur twice as often in women as in men. It is the most common type of headache. Its lifetime prevalence is 30% to 78% in the general population. TTH treatment should be multilevel. It often consists of taking pain medication, muscle relaxants, antidepressants, using biofeedback therapy, acupuncture, and attending behavioral therapy. Several clinical trials also suggest that botulinum toxin (BTX) may be an effective treatment option for such patients. The aim of this study was to evaluate if BTX can be used as a treatment method in TTH in the light of current medical literature. The authors searched the PubMed, EBSCOhost, OVID, Web of Knowledge, Cochrane Library and CINAHL databases to identify relevant publications. The authors finally included 11 papers-prospective and retrospective cohort studies. Among most of the selected studies, there was a significant correlation between using BTX and reduction of TTH pain intensity and severity. By analyzing qualified studies, it can be concluded that botulinum toxin seems to be effective in TTH management.

Botulinum toxin drugs: brief history and outlook.

Science.gov (United States)

Dressler, D

2016-03-01

The global botulinum toxin (BT) market is currently undergoing rapid changes: this may be the time to review the history and the future of BT drug development. Since the early 1990s Botox(®) and Dysport(®) dominated the international BT market. Later, Myobloc(®)/NeuroBloc(®), a liquid BT type B drug, came out, but failed. Xeomin(®) is the latest major BT drug. It features removal of complexing proteins and improved neurotoxin purity. Several new BT drugs are coming out of Korea, China and Russia. Scientific challenges for BT drug development include modification of BT's duration of action, its transdermal transport and the design of BT hybrid drugs for specific target tissues. The increased competition will change the global BT market fundamentally and a re-organisation according to large indication groups, such as therapeutic and cosmetic applications, might occur.

Detection of botulinum toxin types A, B, E, and F activity using the quail embryo

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We recently demonstrated an effective new model for the detection of botulinum toxin type A using quail embryos in place of the mouse model. These experiments demonstrated that the Japanese quail embryo at 15 days of incubation was an effective vertebrate animal model to detect the activity of botu...

Effect of stimulation intensity and botulinum toxin isoform on rat bladder strip contractions.

Science.gov (United States)

Smith, Christopher P; Boone, Timothy B; de Groat, William C; Chancellor, Michael B; Somogyi, George T

2003-07-15

The present experiments compared the inhibitory effects of botulinum toxin A (BoNT-A) and botulinum toxin D (BoNT-D) on neurally evoked contractions of rat bladder strips. We examined the effect of fatigue (trains of 100 shocks at 20Hz every 20s for 10min) followed by non-fatigue stimulation (trains of 100 shocks at 20Hz every 100s for 20min) on the onset of effect and potency of the two toxins. For non-fatigue experiments, strips were untreated (n=4); or incubated with 1.36nM BoNT-A (n=4). During fatigue experiments, strips were untreated (n=5); or treated with either 1.36nM BoNT-A (n=6) or 0.8nM BoNT-D (n=6). In non-fatigue experiments, BoNT-A produced significant decreases in contractile area after 1h of stimulation compared to untreated strips (PD bladder strips, were statistically significant (PD-treated strips, as a significant reduction (PD) and untreated bladder strips responded similarly to atropine, suggesting that the effects of BoNT result from inhibition of both acetylcholine and ATP release. Our results demonstrate that BoNT-D may be a more effective agent to inhibit transmitter release from autonomic nerves of the rat lower urinary tract. Moreover, in our hands, non-fatigue stimulation is as effective as fatigue stimulation in inhibiting bladder strip contractions.

Establishment of alternative potency test for botulinum toxin type A using compound muscle action potential (CMAP) in rats.

Science.gov (United States)

Torii, Yasushi; Goto, Yoshitaka; Nakahira, Shinji; Ginnaga, Akihiro

2014-11-01

The biological activity of botulinum toxin type A has been evaluated using the mouse intraperitoneal (ip) LD50 test. This method requires a large number of mice to precisely determine toxin activity, and, as such, poses problems with regard to animal welfare. We previously developed a compound muscle action potential (CMAP) assay using rats as an alternative method to the mouse ip LD50 test. In this study, to evaluate this quantitative method of measuring toxin activity using CMAP, we assessed the parameters necessary for quantitative tests according to ICH Q2 (R1). This assay could be used to evaluate the activity of the toxin, even when inactive toxin was mixed with the sample. To reduce the number of animals needed, this assay was set to measure two samples per animal. Linearity was detected over a range of 0.1-12.8 U/mL, and the measurement range was set at 0.4-6.4 U/mL. The results for accuracy and precision showed low variability. The body weight was selected as a variable factor, but it showed no effect on the CMAP amplitude. In this study, potency tests using the rat CMAP assay of botulinum toxin type A demonstrated that it met the criteria for a quantitative analysis method. Copyright © 2014 Elsevier Ltd. All rights reserved.

Genetic Diversity Among Botulinum Neurotoxin Producing Clostridial Strains

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Hill, K K; Smith, T J; Helma, C H; Ticknor, L O; Foley, B T; Svennson, R T; Brown, J L; Johnson, E A; Smith, L A; Okinaka, R T; Jackson, P J; Marks, J D

2006-07-06

Clostridium botulinum is a taxonomic designation for many diverse anaerobic spore forming rod-shaped bacteria which have the common property of producing botulinum neurotoxins (BoNTs). The BoNTs are exoneurotoxins that can cause severe paralysis and even death in humans and various other animal species. A collection of 174 C. botulinum strains were examined by amplified fragment length polymorphism (AFLP) analysis and by sequencing of the 16S rRNA gene and BoNT genes to examine genetic diversity within this species. This collection contained representatives of each of the seven different serotypes of botulinum neurotoxins (BoNT A-G). Analysis of the16S rRNA sequences confirmed earlier reports of at least four distinct genomic backgrounds (Groups I-IV) each of which has independently acquired one or more BoNT serotypes through horizontal gene transfer. AFLP analysis provided higher resolution, and can be used to further subdivide the four groups into sub-groups. Sequencing of the BoNT genes from serotypes A, B and E in multiple strains confirmed significant sequence variation within each serotype. Four distinct lineages within each of the BoNT A and B serotypes, and five distinct lineages of serotype E strains were identified. The nucleotide sequences of the seven serotypes of BoNT were compared and show varying degrees of interrelatedness and recombination as has been previously noted for the NTNH gene which is linked to BoNT. These analyses contribute to the understanding of the evolution and phylogeny within this species and assist in the development of improved diagnostics and therapeutics for treatment of botulism.

Botulinum Neurotoxin Injections

Science.gov (United States)

... botulinum neurotoxin as much art as it is science. It is in your best interest to locate the most well-trained and experienced doctor you can find. Before making an appointment to receive botulinum neuro toxin injections, ask the office personnel which doctor ...

Efficacy of a potential trivalent vaccine based on Hc fragments of botulinum toxins A, B, and E produced in a cell-free expression system.

Science.gov (United States)

Zichel, R; Mimran, A; Keren, A; Barnea, A; Steinberger-Levy, I; Marcus, D; Turgeman, A; Reuveny, S

2010-05-01

Botulinum toxins produced by the anaerobic bacterium Clostridium botulinum are the most potent biological toxins in nature. Traditionally, people at risk are immunized with a formaldehyde-inactivated toxin complex. Second generation vaccines are based on the recombinant carboxy-terminal heavy-chain (Hc) fragment of the neurotoxin. However, the materialization of this approach is challenging, mainly due to the high AT content of clostridial genes. Herein, we present an alternative strategy in which the native genes encoding Hc proteins of botulinum toxins A, B, and E were used to express the recombinant Hc fragments in a cell-free expression system. We used the unique property of this open system to introduce different combinations of chaperone systems, protein disulfide isomerase (PDI), and reducing/oxidizing environments directly to the expression reaction. Optimized expression conditions led to increased production of soluble Hc protein, which was successfully scaled up using a continuous exchange (CE) cell-free system. Hc proteins were produced at a concentration of more than 1 mg/ml and purified by one-step Ni(+) affinity chromatography. Mice immunized with three injections containing 5 microg of any of the in vitro-expressed, alum-absorbed, Hc vaccines generated a serum enzyme-linked immunosorbent assay (ELISA) titer of 10(5) against the native toxin complex, which enabled protection against a high-dose toxin challenge (10(3) to 10(6) mouse 50% lethal dose [MsLD(50)]). Finally, immunization with a trivalent HcA, HcB, and HcE vaccine protected mice against the corresponding trivalent 10(5) MsLD(50) toxin challenge. Our results together with the latest developments in scalability of the in vitro protein expression systems offer alternative routes for the preparation of botulinum vaccine.

Update on botulinum neurotoxin use in aesthetic dermatology.

Science.gov (United States)

Ibrahim, Omer; Keller, Emily C; Arndt, Kenneth A

2014-12-01

Botulinum toxins are among the most widely studied and versatile drugs in the medicinal market. Since their extraction from Clostridium botulinum, they have been harnessed and incorporated into different formulations with varied properties and actions. These products have been used to treat countless disorders such as musculoskeletal disorders, headaches, and eye disorders, among many others. In the realm of aesthetic cutaneous medicine, the evolution and creativity in the use of botulinum toxins has been swift and ever changing. Knowledge of the science and innovation behind this toxin enables the user to provide the patient with a variety of treatment options founded in evidence-based medicine. This review will highlight the properties and actions of the newer, more recent neurotoxin preparations, as well as some of the latest and novel therapeutic applications of botulinum toxins.

Advances in Assays and Analytical Approaches for Botulinum Toxin Detection

Energy Technology Data Exchange (ETDEWEB)

Grate, Jay W.; Ozanich, Richard M.; Warner, Marvin G.; Bruckner-Lea, Cindy J.; Marks, James D.

2010-08-04

Methods to detect botulinum toxin, the most poisonous substance known, are reviewed. Current assays are being developed with two main objectives in mind: 1) to obtain sufficiently low detection limits to replace the mouse bioassay with an in vitro assay, and 2) to develop rapid assays for screening purposes that are as sensitive as possible while requiring an hour or less to process the sample an obtain the result. This review emphasizes the diverse analytical approaches and devices that have been developed over the last decade, while also briefly reviewing representative older immunoassays to provide background and context.

Vitreous hemorrhage and Rhegmatogenous retinal detachment that developed after botulinum toxin injection to the extraocular muscle: case report.

Science.gov (United States)

Lee, Dong Hyun; Han, Jinu; Han, Sueng-Han; Lee, Sung Chul; Kim, Min

2017-12-13

The authors report a case of a rare complication that occurred after botulinum toxin injection to the extraocular muscle, which was easily overlooked and successfully corrected by surgery. A 34-year-old female patient visited our clinic for diplopia and ocular motility disorder after removal of an epidermoid tumor of the brain. At her initial visit, her best-corrected visual acuity (BCVA) was 20/20 for both eyes. An alternate cover test showed 45 prism-diopter esotropia and 3 prism-diopter hypertropia in the right eye. Following 6 months of observation, the deviation of the strabismus did not improve, and botulinum toxin was injected into the right medial rectus (RMR). After 6 days, she visited our clinic with decreased visual acuity of her right eye. The BCVA was found to be 20/50 for her right eye. Funduscopic examination presented a retinal tear inferonasal to the optic disc with preretinal hemorrhage. Subretinal fluid nasal to the fovea was seen on optical coherence tomography (OCT). Barrier laser photocoagulation was done around the retinal tear; however, her visual acuity continued to decrease, and vitreous hemorrhage and subretinal fluid at the lesion did not improve. In addition, a newly developed epiretinal membrane was seen on OCT. An alternate cover test presented 30 prism-diopter right esotropia. 19 weeks after RMR botulinum toxin injection, she received pars plana vitrectomy, membranectomy, endolaser barrier photocoagulation, and intravitreal bevacizumab (Avastin®) injection. After 4 months, her visual acuity improved to 20/20, and only 4 prism-diopter of right hypertropia and 3 prism-diopter of exotropia were noted. Vitreous opacity and the epiretinal membrane were completely removed, as confirmed by funduscopic and examination. Sudden loss of vision after injection of botulinum toxin into the extraocular muscle may suggest a serious complication, and a prompt, thorough ophthalmic examination should be performed. If improvements are not observed

Integrated bioassays in microfluidic devices: botulinum toxin assays.

Science.gov (United States)

Mangru, Shakuntala; Bentz, Bryan L; Davis, Timothy J; Desai, Nitin; Stabile, Paul J; Schmidt, James J; Millard, Charles B; Bavari, Sina; Kodukula, Krishna

2005-12-01

A microfluidic assay was developed for screening botulinum neurotoxin serotype A (BoNT-A) by using a fluorescent resonance energy transfer (FRET) assay. Molded silicone microdevices with integral valves, pumps, and reagent reservoirs were designed and fabricated. Electrical and pneumatic control hardware were constructed, and software was written to automate the assay protocol and data acquisition. Detection was accomplished by fluorescence microscopy. The system was validated with a peptide inhibitor, running 2 parallel assays, as a feasibility demonstration. The small footprint of each bioreactor cell (0.5 cm2) and scalable fluidic architecture enabled many parallel assays on a single chip. The chip is programmable to run a dilution series in each lane, generating concentration-response data for multiple inhibitors. The assay results showed good agreement with the corresponding experiments done at a macroscale level. Although the system has been developed for BoNT-A screening, a wide variety of assays can be performed on the microfluidic chip with little or no modification.

Botulinum toxin A versus B in sialorrhea: a prospective, randomized, double-blind, crossover pilot study in patients with amyotrophic lateral sclerosis or Parkinson's disease.

Science.gov (United States)

Guidubaldi, Arianna; Fasano, Alfonso; Ialongo, Tamara; Piano, Carla; Pompili, Maurizio; Mascianà, Roberta; Siciliani, Luisa; Sabatelli, Mario; Bentivoglio, Anna Rita

2011-02-01

Either botulinum toxins (BoNTs) A and B have been used for improving drooling in different neurological conditions. Consecutive patients affected by Amyotrophic Lateral Sclerosis (ALS) or Parkinson's Disease (PD) accompanied by severe drooling were randomized to receive botulinum neurotoxin type A (BoNT-A) or B (BoNT-B) injections into the salivary glands. Following the first treatment, when sialorrhea returned to baseline (at least three months after the first injection), subjects were re-treated with the other serotype. Ultrasound-guided injections into parotid and submandibular glands were bilaterally performed: total doses were 250 U BoNT-A (Dysport) and 2500 U BoNT-B (Neurobloc). Objective (cotton roll weight) and subjective (ad hoc clinical scales) evaluations were performed at baseline, after 1 and 4 weeks, and every 4 weeks until drooling returned to baseline. Twenty-seven patients (15 ALS and 12 PD) were enrolled, fourteen completed the study. BoNT-A and BoNT-B treatments gave both subjective and objective improvements in all patients. The latency was significantly shorter after BoNT-B treatments (3.2 ± 3.7 days) compared to BoNT-A (6.6 ± 4.1 days; P = 0.002). The mean benefit duration was similar at 75 and 90 days for BoNT-A and BoNT-B, respectively (P = NS). The only toxin-related side effect was a change to saliva thickness. Either 250 U Dysport or 2500 U Neurobloc have similar effectiveness and safety in controlling sialorrhea. BoNT-B has a shorter latency and comparable duration. Cost analysis, considering the doses used in this study protocol favored BoNT-B treatment. Copyright © 2010 Movement Disorder Society.

Channels formed by botulinum, tetanus, and diphtheria toxins in planar lipid bilayers: relevance to translocation of proteins across membranes.

OpenAIRE

Hoch, D H; Romero-Mira, M; Ehrlich, B E; Finkelstein, A; DasGupta, B R; Simpson, L L

1985-01-01

The heavy chains of both botulinum neurotoxin type B and tetanus toxin form channels in planar bilayer membranes. These channels have pH-dependent and voltage-dependent properties that are remarkably similar to those previously described for diphtheria toxin. Selectivity experiments with anions and cations show that the channels formed by the heavy chains of all three toxins are large; thus, these channels could serve as "tunnel proteins" for translocation of active peptide fragments. These f...

Botulinum Toxin-A Dosing Trends for Adductor Spasmodic Dysphonia at a Single Institution Over 10 Years.

Science.gov (United States)

Bradley, Joseph P; Barrow, Emily M; Hapner, Edie R; Klein, Adam M; Johns, Michael M

2017-05-01

This study aimed to identify the changes in dosing of botulinum toxin-A for adductor spasmodic dysphonia (ADSD) over a prolonged period. This is a retrospective chart review. One hundred thirteen subjects treated for ADSD from 2003 to 2013 were identified from a clinical database. Subject age, gender, and total injection dose amount were all recorded for all subjects who had at least 10 injections. Fifty-four subjects met criteria for inclusion. There were no age or gender differences in the starting dose for subjects. Dosing decreased significantly compared with the second dose (5.05 ± 1.623 Units), by the sixth dose (4.26 ± 1.698 Units), and continued through the 10th dose (4.08 ± 2.019 Units) (P < 0.005 for all). Botulinum toxin-A dosing for ADSD decreases consistently over subsequent injections after the initial two dose titrations. Copyright © 2017. Published by Elsevier Inc.

The use of botulinum toxin A in the treatment of functional epiphora.

Science.gov (United States)

Whittaker, Karl W; Matthews, Bethan N; Fitt, Alan W; Sandramouli, S

2003-09-01

The purpose of this study was to investigate the hitherto undescribed effects of botulinum toxin A injected into the lacrimal gland in patients with functional epiphora. A prospective non-comparative interventional case series study was designed to include patients with functional epiphora who presented to the Oculoplastic unit at the Wolverhampton and Midland Counties Eye Infirmary. Botulinum toxin A (2.5-5 units) was injected into the palpebral lobe of the lacrimal gland on the worst affected side via a transconjunctival approach under topical anaesthesia. Patients underwent a Schirmer test and provided a subjective evaluation of their epiphora symptoms, indoors and outdoors, at baseline and at 1, 4 and 13 weeks after injection. The mean score for symptoms indoors and outdoors was calculated. Fourteen patients agreed to take part in the study. Subjective epiphora scores improved in 8 out of the 11 patients (72.7%) who completed 13 weeks of follow-up. Schirmer test results showed objective reduction in tearing from baseline but did not strongly correlate with the subjective epiphora scores. Transient mild ptosis and diplopia were experienced by two patients. The results from this small pilot study are encouraging, although larger, controlled trials are needed to assess the optimal dose of BTX-A, its long-term efficacy and safety, and the role of multiple injections.

Botulinum toxin A, brain and pain.

Science.gov (United States)

Matak, Ivica; Lacković, Zdravko

2014-01-01

Botulinum neurotoxin type A (BoNT/A) is one of the most potent toxins known and a potential biological threat. At the same time, it is among the most widely used therapeutic proteins used yearly by millions of people, especially for cosmetic purposes. Currently, its clinical use in certain types of pain is increasing, and its long-term duration of effects represents a special clinical value. Efficacy of BoNT/A in different types of pain has been found in numerous clinical trials and case reports, as well as in animal pain models. However, sites and mechanisms of BoNT/A actions involved in nociception are a matter of controversy. In analogy with well known neuroparalytic effects in peripheral cholinergic synapses, presently dominant opinion is that BoNT/A exerts pain reduction by inhibiting peripheral neurotransmitter/inflammatory mediator release from sensory nerves. On the other hand, growing number of behavioral and immunohistochemical studies demonstrated the requirement of axonal transport for BoNT/A's antinociceptive action. In addition, toxin's enzymatic activity in central sensory regions was clearly identified after its peripheral application. Apart from general pharmacology, this review summarizes the clinical and experimental evidence for BoNT/A antinociceptive activity and compares the data in favor of peripheral vs. central site and mechanism of action. Based on literature review and published results from our laboratory we propose that the hypothesis of peripheral site of BoNT/A action is not sufficient to explain the experimental data collected up to now. Copyright © 2014 Elsevier Ltd. All rights reserved.

Botulinum toxin injections for new onset bilateral vocal fold motion impairment in adults.

Science.gov (United States)

Ekbom, Dale C; Garrett, C Gaelyn; Yung, Katherine C; Johnson, Felicia L; Billante, Cheryl R; Zealear, David L; Courey, Mark S

2010-04-01

Review of clinical experience and results using botulinum toxin type A (BTX) for the management of adult patients with respiratory compromise due to new onset bilateral vocal fold motion impairment (BVFMI). Retrospective case series. The records of 11 patients from two institutions with respiratory compromise due to bilateral vocal fold motion impairment were reviewed. Age, sex, etiology of motion impairment, subjective response to BTX injections, changes in pulmonary function studies pre- and postinjection when available, the dosage of botulinum toxin required to achieve response, the number of injections per patient, and complications were reported. All patients were over 18 years old. There were three male and eight female subjects. The etiology of BVFMI was due to previous anterior cervical surgery in nine patients and prolonged intubation in two. Ten patients reported symptomatic improvement and returned for an average of nine injections over the 10-year period of study. The most common interval between injections was 3 months. In all patients the dose required to achieve symptomatic improvement was at least 2.5 mouse units injected into each vocal fold. One patient without relief of symptoms had bilateral cricoarytenoid joint fixation. Complications were limited to moderate dysphagia in one patient and breathy dysphonia in all patients. BTX injection into the vocal folds provides temporary relief of symptoms in airway obstruction in adult patients with BVFMI. Patients require an average of 2.5 units of botulinum injection into each vocal fold and have an average length of response of 3 months. BTX injection may be used as a form of temporary relief of airway obstruction in patients wishing to avoid ablative surgery or tracheotomy.

Off Label Use of Botulinum Toxin in Children under Two Years of Age: A Systematic Review

Directory of Open Access Journals (Sweden)

Claudia Druschel

2013-01-01

Full Text Available The treatment of children with cerebral palsy with Botulinum Toxin is considered safe and effective, but is only approved for children older than two years of age. The effect of BoNT-A injection on juvenile skeletal muscle especially on neuromuscular junction density, distribution and morphology is poorly delineated and concerns of irreversible damage to the motor endplates especially in young children exist. In contrast, earlier treatment could be appropriate to improve the attainment of motor milestones and general motor development. This review systematically analyzes the evidence regarding this hypothesis. A database search, including PubMed and Medline databases, was performed and all randomized controlled trials (RCTs comparing the efficacy of Botulinum Toxin in children younger than two years were identified. Two authors independently extracted the data and the methods of all identified trials were assessed. Three RCTs met the inclusion criteria. The results of the analysis revealed an improvement in spasticity of the upper and lower extremities as well as in the range of motion in the joints of the lower limbs. However, evidence of an improvement of general motor development could not be found, as the assessment of this area was not completely specified for this patient group. Based on available evidence it can not be concluded that Botulinum Toxin treatment in children younger than two years improves the achievement of motor milestones. However, there is evidence for the reduction of spasticity, avoiding contractures and delaying surgery. Due to some limitations, the results of this review should be cautiously interpreted. More studies, long-term follow up independent high-quality RCTs with effectiveness analyses are needed.

Crystal Structure of the Receptor-Binding Domain of Botulinum Neurotoxin Type HA, Also Known as Type FA or H

OpenAIRE

Yao, Guorui; Lam, Kwok-ho; Perry, Kay; Weisemann, Jasmin; Rummel, Andreas; Jin, Rongsheng

2017-01-01

Botulinum neurotoxins (BoNTs), which have been exploited as cosmetics and muscle-disorder treatment medicines for decades, are well known for their extreme neurotoxicity to humans. They pose a potential bioterrorism threat because they cause botulism, a flaccid muscular paralysis-associated disease that requires immediate antitoxin treatment and intensive care over a long period of time. In addition to the existing seven established BoNT serotypes (BoNT/A–G), a new mosaic toxin type termed Bo...

A botulinum toxin A treatment algorithm for de novo management of torticollis and laterocollis

Science.gov (United States)

Kupsch, Andreas; Müngersdorf, Martina; Paus, Sebastian; Stenner, Andrea; Jost, Wolfgang

2011-01-01

Objectives Few studies have investigated the injection patterns for botulinum toxin type A for the treatment of heterogeneous forms of cervical dystonia (CD). This large, prospective, open-label, multicentre study aimed to evaluate the effectiveness and safety of 500 U botulinum toxin A for the initial treatment according to a standardised algorithm of the two most frequent forms of CD, predominantly torticollis and laterocollis. Design Patients (aged ≥18 years) with CD not previously treated with botulinum neurotoxin therapy were given one treatment with 500 U Dysport, according to a defined intramuscular injection algorithm based on clinical assessment of direction of head deviation, occurrence of shoulder elevation, occurrence of tremor (all evaluated using the Tsui rating scale) and hypertrophy of the sternocleidomastoid muscle. Results In this study, 516 patients were enrolled, the majority of whom (95.0%) completed treatment. Most patients had torticollis (78.1%). At week 4, mean Tsui scores had significantly decreased by −4.01, −3.76 and −4.09 points in the total, torticollis and laterocollis populations, respectively. Symptom improvement was equally effective between groups. Tsui scores remained significantly below baseline at week 12 in both groups. Treatment was well tolerated; the most frequent adverse events were muscular weakness (13.8%), dysphagia (9.9%) and neck pain (6.6%). Conclusions Dysport 500 U is effective and well tolerated for the de novo management of a range of heterogeneous forms of CD, when using a standardised regimen that allows tailored dosing based on individual symptom assessment. Clinical trials information (NCT00447772; clinicaltrials.gov) PMID:22021883

Cutaneous cooling to manage botulinum toxin injection-associated pain in patients with facial palsy: A randomised controlled trial.

Science.gov (United States)

Pucks, N; Thomas, A; Hallam, M J; Venables, V; Neville, C; Nduka, C

2015-12-01

Botulinum toxin injections are an effective, well-established treatment to manage synkinesis secondary to chronic facial palsy, but they entail painful injections at multiple sites on the face up to four times per year. Cutaneous cooling has long been recognised to provide an analgesic effect for cutaneous procedures, but evidence to date has been anecdotal or weak. This randomised controlled trial aims to assess the analgesic efficacy of cutaneous cooling using a cold gel pack versus a room-temperature Control. The analgesic efficacy of a 1-min application of a Treatment cold (3-5 °C) gel pack versus a Control (room-temperature (20 °C)) gel pack prior to botulinum toxin injection into the platysma was assessed via visual analogue scale (VAS) ratings of pain before, during and after the procedure. Thirty-five patients received both trial arms during two separate clinic appointments. Cold gel packs provided a statistically significant reduction in pain compared with a room-temperature Control (from 26.4- to 10.2-mm VAS improvement (p injected or the order in which the Treatment or Control gel packs were applied. Cryoanalgesia using a fridge-cooled gel pack provides an effective, safe and cheap method for reducing pain at the botulinum toxin injection site in patients with facial palsy. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Identification of RNA species in the RNA-toxin complex and structure of the complex in Clostridium botulinum type E.

Science.gov (United States)

Kitamura, Masaru

2002-02-15

Clostridium botulinum type E toxin was isolated in the form of a complex with RNA(s) from bacterial cells. Characterization of the complexed RNA remains to be elucidated. The RNA is identified here as ribosomal RNA (rRNA) having 23S and 16S components. The RNA-toxin complexes were found to be made up of three types with different molecular sizes. The three types of RNA-toxin complex are toxin bound to both the 23S and 16S rRNA, toxin bound to the 16S rRNA and a small amount of 23S rRNA, and toxin bound only to the 16S rRNA. ©2002 Elsevier Science (USA).

Use of botulinum toxin in musculoskeletal pain [v2; ref status: indexed, http://f1000r.es/16j

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Jasvinder A Singh

2013-07-01

Full Text Available Chronic musculoskeletal pain is a common cause of chronic pain, which is associated with a total cost of $635 billion per year in the U.S. Emerging evidence suggests an anti-nociceptive action of botulinum toxin, independent of its muscle paralyzing action. This review provides a summary of data from both non-randomized and randomized clinical studies of botulinum toxin in back pain and various osteoarticular conditions, including osteoarthritis, tennis elbow, low back pain and hand pain. Three randomized controlled trials (RCTs of small sizes provide evidence of short-term efficacy of a single intra-articular injection of 100 units of botulinum toxin A (BoNT/A for the relief of pain and the improvement of both function and quality of life in patients with chronic joint pain due to arthritis. Three RCTs studied intramuscular BoNT/A for tennis elbow with one showing a significant improvement in pain relief compared with placebo, another one showing no difference from placebo, and the third finding that pain and function improvement with BoNT/A injection were similar to those obtained with surgical release. One RCT of intramuscular BoNT/A for low back pain found improvement in pain and function compared to placebo. Single RCTs using local injections of BoNT in patients with either temporomandibular joint (TMJ pain or plantar fasciitis found superior efficacy compared to placebo. One RCT of intramuscular BoNT/B in patients with hand pain and carpal tunnel syndrome found improvement in pain in both BoNT/B and placebo groups, but no significant difference between groups. Most evidence is based on small studies, but the use of BoNT is supported by a single, and sometimes up to three, RCTs for several chronic musculoskeletal pain conditions. This indicates that botulinum toxin may be a promising potential new treatment for chronic refractory musculoskeletal pain. Well-designed large clinical trials are needed.

ADP-ribosylation of actins in fibroblasts and myofibroblasts by botulinum C2 toxin: Influence on microfilament morphology and migratory behavior

DEFF Research Database (Denmark)

Rønnov-Jessen, Lone; Petersen, Ole William

1996-01-01

botulinum C2 toxin. The substrate for C2 toxin is globular actin, which upon ribosylation cannot incorporate into microfilaments. The pattern of actin ADP-ribosylation in (myo)fibroblasts in the presence of [32P]NAD was analyzed by isoelectric focusing, fluorography and immunoblotting. The influence of C2...... toxin on microfilaments in intact cells was further assessed by immunofluorescence, and motility was measured in a mass migration assay and by computerized video time-lapse microscopy. We show here that C2 toxin specifically ribosylates - and -actin in both fibroblasts and myofibroblasts. Whereas...

A comparative trial of ice application versus EMLA cream in alleviation of pain during botulinum toxin injections for palmar hyperhidrosis.

Science.gov (United States)

Alsantali, Adel

2018-01-01

Botulinum toxin is a safe and effective therapy for palmar hyperhidrosis, but the associated pain from injections limits the usefulness of this method of treatment. To evaluate the efficacy of Eutectic Mixture of Local Anesthetics (EMLA) cream versus ice application in alleviation of pain during botulinum toxin injections for palmar hyperhidrosis. In this prospective study, 23 patients underwent palm Botox injections to treat their excessive sweating. In each patient, EMLA cream was applied to one palm and ice was applied directly before the injections in the other palm. Pain was evaluated using a Visual Analog Scale. Statistically, there was a significant difference in pain control between EMLA cream group and ice application group ( p cream was applied was 8.9 (SD=0.81), whereas it was 4.8 (±0.9) in the ice group. In this study, the successful use of ice application in reducing pain by 40% in comparison to EMLA cream during Botox toxin injection for palmar hyperhidrosis is demonstrated.

Botulinum toxin as treatment for focal dystonia : a systematic review of the pharmaco-therapeutic and pharmaco-economic value

NARCIS (Netherlands)

Zoons, E.; Dijkgraaf, M. G. W.; Dijk, J. M.; van Schaik, I. N.; Tijssen, M. A.

2012-01-01

Focal dystonia is a common, invalidating neurologic condition characterized by involuntary, sustained muscle contractions causing twisting movements and abnormal postures in one body part. Currently, botulinum toxin is the treatment of first choice. We performed a systematic review towards the

Botulinum toxin as treatment for focal dystonia: a systematic review of the pharmaco-therapeutic and pharmaco-economic value

NARCIS (Netherlands)

Zoons, E.; Dijkgraaf, M. G. W.; Dijk, J. M.; van Schaik, I. N.; Tijssen, M. A.

2012-01-01

Focal dystonia is a common, invalidating neurologic condition characterized by involuntary, sustained muscle contractions causing twisting movements and abnormal postures in one body part. Currently, botulinum toxin is the treatment of first choice. We performed a systematic review towards the

Analgesic Effects of Botulinum Toxin in Children with CP

DEFF Research Database (Denmark)

Sandahl Michelsen, Josephine; Normann, Gitte; Wong, Christian

2018-01-01

Experiencing pain is the greatest contributor to a reduced quality of life in children with cerebral palsy (CP). The presence of pain is quite common (~60%) and increases with age. This leads to missed school days, less participation, and reduced ambulation. Despite these alarming consequences...... of disorders and could potentially have an analgesic effect in children with CP as well. Even though most of the studies presented here show promising results, many also have limitations in their methodology as it is unlikely to capture all dimensions of pain in this heterogeneous group using only one...... assessment tool. In this review, we present a new way of examining the analgesic effect of botulinum toxin in children with CP using a variety of pain scores....

The Effect of Intramural Botulinum Toxin Injections on the Elongation of the Piglet Oesophagus Is Time Dependent

DEFF Research Database (Denmark)

Bakholdt Dibbern, Christian; Rose, Morten; Ellebæk, Mark Bremholm

2017-01-01

Introduction One in 4,000 infants is born with oesophageal atresia. Approximately 15% of these have a long gap oesophageal atresia, where primary anastomosis is difficult or impossible. Previous studies have shown an effect of intramural botulinum toxin type A (BTX-A) injections on the elongation...

Potent New Small-Molecule Inhibitor of Botulinum Neurotoxin Serotype A Endopeptidase Developed by Synthesis-Based Computer-Aided Molecular Design

Science.gov (United States)

2009-11-01

simulations; (4) synthesis and evaluation of the molecules from Step 2 or 3 (e.g., synthesizing and testing AHP). From synthetic chemistry point of view...2000) Synthesis of 6H-indolo [2,3-b][1,6]naphthyridines and related compounds as the 5-Aza analogues of ellipticine alkaloids . J Org Chem 65: 7977–7983...Potent New Small-Molecule Inhibitor of Botulinum Neurotoxin Serotype A Endopeptidase Developed by Synthesis -Based Computer-Aided Molecular Design

Efficacy and Safety of IncobotulinumtoxinA in Subjects Previously Treated with Botulinum Toxin versus Toxin-Naïve Subjects with Cervical Dystonia

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Hubert Fernandez

2013-05-01

Full Text Available Background: To determine whether botulinum toxin treatment history affected the outcomes of a study comparing the safety and efficacy of incobotulinumtoxinA with placebo in subjects with cervical dystonia (CD.Methods: This was a prospective, double‐blind, randomized, placebo‐controlled, multicenter trial in botulinum toxin‐treated or toxin‐naïve CD subjects. Subjects received a fixed dose of either 120 U or 240 U of incobotulinumtoxinA or placebo. The primary outcome measure was change from baseline to Week 4 in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS total score. Treatment‐emergent adverse events (TEAEs were also evaluated. This report represents a subgroup analysis of botulinum toxin‐treated or toxin‐naïve subjects.Results: Participants (N = 233; 38.6% toxin‐naïve had a mean age of 52.8 years. IncobotulinumtoxinA significantly improved TWSTRS total scores from baseline to Week 4 in both dose groups versus placebo, and the improvement persisted through the end of the study (≤20 weeks. Both the previously toxin‐treated and toxin‐naïve subjects demonstrated significant improvements in TWSTRS total scores at Week 4 compared to baseline. The most frequent TEAEs in the incobotulinumtoxinA groups were dysphagia, neck pain, and muscular weakness, which were generally mild. TEAEs were more common in the 240 U group and toxin‐naïve subjects. Discussion: Overall, incobotulinumtoxinA was safe and effective in CD, regardless of toxin therapy history. A lower starting dose may be better tolerated among toxin‐naïve subjects without sacrificing efficacy.

Characterization of SNARE Cleavage Products Generated by Formulated Botulinum Neurotoxin Type-A Drug Products

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Jack Xie

2010-08-01

Full Text Available The study evaluated substrate cleavage product(s generated by three botulinum neurotoxin serotype A (BoNT/A medicinal drug products utilizing a novel and highly specific, light-chain activity, high-performance liquid chromatography (LCA-HPLC method. Samples were reacted with a commercially available BoNT/A fluorescent substrate derived from the SNAP-25 sequence. Reaction products were separated by reversed-phase HPLC. The method detected an atypical cleavage pattern by one of the formulated drug products. IncobotulinumtoxinA produced two cleavage fragments rather than the single fragment typically generated by BoNT/A. Identification confirmed the secondary cleavage at a position corresponding to SNAP-25 Arg198–Ala199 (normal BoNT/A cleavage is Gln197–Arg198. Arg198–Ala199 is also the cleavage site for trypsin and serotype C toxin. Normal cleavage was observed for all other BoNT/A drug product samples, as well as 900-kD and 150-kD bulk toxin BoNT/A. The reason for this unexpected secondary cleavage pattern by one formulated BoNT/A drug product is unknown. Possible explanations include a contaminating protease and/or damage to the 150-kD type-A toxin causing nonspecific substrate recognition and subsequent cleavage uncharacteristic of type-A toxin. The BoNT/A drug products were also analyzed via the LCA-HPLC assay using a commercial BoNT/C fluorescent substrate derived from the syntaxin sequence. Cleavage of the serotype C substrate by incobotulinumtoxinA was also confirmed whilst neither of the other drug products cleaved the syntaxin substrate.

Dramatic changes in muscle contractile and structural properties after 2 botulinum toxin injections.

Science.gov (United States)

Minamoto, Viviane B; Suzuki, Kentaro P; Bremner, Shannon N; Lieber, Richard L; Ward, Samuel R

2015-10-01

Botulinum toxin is frequently administered serially to maintain therapeutic muscle paralysis, but the effect of repeated doses on muscle function are largely unknown. This study characterized the muscle response to 2 onabotulinum toxin (BoNT) injections separated by 3 months. Animal subjects received a single toxin injection (n = 8), 2 BoNT injections separated by 3 months (n = 14), or 1 BoNT and 1 saline injection separated by 3 months (n = 8). The functional effect of 2 serial injections was exponentially greater than the effect of a single injection. While both groups treated with a single BoNT injection had decreased torque in the injected leg by approximately 50% relative to contralateral legs, the double BoNT injected group had decreased torque by over 95% relative to the preinjection level. Both single and double BoNT injections produced clear signs of fiber-type grouping. These experiments demonstrate a disproportionately greater effect of repeated BoNT injections. © 2015 Wiley Periodicals, Inc.

Rapid Detection of Clostridium botulinum Toxins A, B, E, and F in Clinical Samples, Selected Food Matrices, and Buffer Using Paramagnetic Bead-Based Electrochemiluminescence Detection

National Research Council Canada - National Science Library

Rivera, Victor R; Gamez, Frank J; Keener, William K; White, Jill A; Poli, Mark A

2006-01-01

Sensitive and specific electrochemiluminescence (ECL) assays were used to detect Clostridium botulinum neurotoxins serotypes A, B, E, and F in undiluted human serum, undiluted human urine, assay buffer, and selected food matrices...

Epitope-Targeting of Tertiary Protein Structure Enables Target-Guided Synthesis of a Potent in Cell Inhibitor of Botulinum Neurotoxin**

OpenAIRE

Farrow, Blake; Wong, Michelle; Malette, Jacquie; Lai, Bert; Deyle, Kaycie M.; Das, Samir; Nag, Arundhati; Agnew, Heather D.; Heath, James R.

2015-01-01

Botulinum neurotoxin (BoNT) serotype A is the most lethal known toxin and has an occluded structure, which prevents direct inhibition of its active site before it enters the cytosol. Target-guided synthesis by in situ click chemistry is combined with synthetic epitope targeting to exploit the tertiary structure of the BoNT protein as a landscape for assembling a competitive inhibitor. A substrate-mimicking peptide macrocycle is used as a direct inhibitor of BoNT. An epitope-targeting in situ ...

Crystallization and preliminary X-ray analysis of the HA3 component of Clostridium botulinum type C progenitor toxin

Energy Technology Data Exchange (ETDEWEB)

Nakamura, Toshio; Tonozuka, Takashi; Kotani, Mao; Obata, Kanae [Department of Applied Biological Science, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Oguma, Keiji [Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558 (Japan); Nishikawa, Atsushi, E-mail: nishikaw@cc.tuat.ac.jp [Department of Applied Biological Science, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); CREST, Japan Science and Technology Agency (Japan)

2007-12-01

HA3, a 70 kDa haemagglutinating protein, is a precursor form of HA3a and HA3b, the subcomponents of Clostridium botulinum type C 16S progenitor toxin. In this report, recombinant HA3 protein was overexpressed in Escherichia coli, purified and crystallized. HA3, a 70 kDa haemagglutinating protein, is a precursor form of HA3a and HA3b, the subcomponents of Clostridium botulinum type C 16S progenitor toxin. In this report, recombinant HA3 protein was overexpressed in Escherichia coli, purified and crystallized. Diffraction data were collected to 2.6 Å resolution and the crystal belonged to the hexagonal space group P6{sub 3}. Matthews coefficient and self-rotation function calculations indicate that there is probably one molecule of HA3 in the asymmetric unit. A search for heavy-atom derivatives has been undertaken.

Botulinum toxin type A injections for the management of muscle tightness following total hip arthroplasty: a case series

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Delanois Ronald E

2009-08-01

Full Text Available Abstract Background Development of hip adductor, tensor fascia lata, and rectus femoris muscle contractures following total hip arthroplasties are quite common, with some patients failing to improve despite treatment with a variety of non-operative modalities. The purpose of the present study was to describe the use of and patient outcomes of botulinum toxin injections as an adjunctive treatment for muscle tightness following total hip arthroplasty. Methods Ten patients (14 hips who had hip adductor, abductor, and/or flexor muscle contractures following total arthroplasty and had been refractory to physical therapeutic efforts were treated with injection of botulinum toxin A. Eight limbs received injections into the adductor muscle, 8 limbs received injections into the tensor fascia lata muscle, and 2 limbs received injection into the rectus femoris muscle, followed by intensive physical therapy for 6 weeks. Results At a mean final follow-up of 20 months, all 14 hips had increased range in the affected arc of motion, with a mean improvement of 23 degrees (range, 10 to 45 degrees. Additionally all hips had an improvement in hip scores, with a significant increase in mean score from 74 points (range, 57 to 91 points prior to injection to a mean of 96 points (range, 93 to 98 at final follow-up. There were no serious treatment-related adverse events. Conclusion Botulinum toxin A injections combined with intensive physical therapy may be considered as a potential treatment modality, especially in difficult cases of muscle tightness that are refractory to standard therapy.

Comparison of clinical marking and ultrasound-guided injection of Botulinum type A toxin into the masseter muscles for treating bruxism and its cosmetic effects.

Science.gov (United States)

Quezada-Gaon, Natacha; Wortsman, Ximena; Peñaloza, Osvaldo; Carrasco, Juan Eduardo

2016-09-01

Botulinum toxin type A has been used for treating the hypertrophy of the masseter muscles and its cosmetic effects. Ultrasound is increasingly used in dermatology, along with the guidance of mini-invasive procedures. To evaluate the role of ultrasound for guiding the application of Botulinum A toxin in patients with cosmetic alterations due to bruxism, correlate the clinical landmarks with the ultrasound findings, and study the effect on the symptoms, cosmetics, and quality of life. Twenty individuals with bruxism and cosmetic alterations underwent an ultrasound-guided injection of Botulinum toxin type A in each masseter muscle. Clinical and ultrasound marking of the procedure was compared. Clinical and sonographic evaluation was performed at the time of injection and 3 months later. Ten normal individuals underwent ultrasound of the masseter muscles as a control group. Up to 65% of individuals showed anatomical variants of the salivary glands. The method for clinically marking the skin showed a frequently erroneous location of the anterior point (up to 40% of cases) that was proven by ultrasound to be out of the muscle. In 20% of cases, ultrasound showed that the needle should be longer to enter the muscle. After injection, most of the patients demonstrated a decrease of the symptoms and cosmetic and quality of life improvements. Ultrasound can be a potent tool for guiding the injection of Botulinum toxin into the masseter muscles. It may contribute to a more personalized procedure, better cosmetic results, and help to avoid potential complications. © 2016 Wiley Periodicals, Inc.

Effect of botulinum toxin A and nitroglycerin on random skin flap survival in rats.

Science.gov (United States)

Ghanbarzadeh, Kourosh; Tabatabaie, Omid Reza; Salehifar, Ebrahim; Amanlou, Massoud; Khorasani, Ghasemali

2016-01-01

A suitable pharmacological substitute for the well-established surgical delay technique for random skin flaps to increase viability has been elusive. To evaluate the effects of nitroglycerin and botulinum toxin type A on random flap survival in a rat model. The present controlled experimental study was performed in the four groups of rats. One week after intervention in each group, the flap was raised and kept in situ, and flap necrosis was evaluated through follow-up. Group 1 received intradermal botulinum toxin type A (BTX-A) and topical nitroglycerin 2%; group 2 received BTX-A and topical Vaseline (Unilever, USA); group 3 received topical nitroglycerin and intradermal normal saline; and group 4 received topical Vaseline and intradermal normal saline. BTX-A reduced the area of necrosis compared with control (24% versus 56% respectively; P<0.001). Nitroglycerin application was associated with a trend toward improved flap viability (42% versus 56%; P=0.059). The combination of topical nitroglycerin and BTX-A, compared with Vaseline and BTX-A, was associated with decreased flap necrosis (16.1% versus 24%, respectively), although it was not statistically significant (P=0.45). BTX-A was effective in reducing distal flap necrosis. The effect of BTX-A was significantly more pronounced than nitroglycerin ointment.

Toxina botulínica y su empleo en la patología oral y maxilofacial Botulinum toxin and its use in oral and maxillofacial pathology

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D. Martínez-Pérez

2004-06-01

Full Text Available Resumen: Las toxinas botulínicas son exotoxinas de la bacteria formadora de esporas Clostridim botulinum y los agentes causantes del botulismo. Cuando se inyecta en el músculo produce una parálisis flácida. El efecto clínico está directamente relacionado con la dosis y debe ajustarse para cada caso concreto. La Toxina botulínica ha demostrado en los más de veinte años en que se está utilizando que es un fármaco seguro. Las indicaciones de la toxina botulínica en la actualidad incluyen todas aquellas patologías que resultan de la hiperfunción muscular y la disfunción autonómica.Abstract: Botilinum toxins are exotoxins of the bacteria that form the Clostridium botulinum spores and the causative agents of botulism. When injected into the muscle flaccid paralysis is produced. The clinical effect is directly related with the dose and is should be adjusted for each particular case. over the last twenty years that it has been in use, the botulinum toxin has shown itself to be a reliable drug. Current indications for the use of botulinum toxin include all those pathologies which are the results of muscle hyperfunction and autonomic dysfunction.

Botulinum Toxin Type A as Preoperative Treatment for Immediately Loaded Dental Implants Placed in Fresh Extraction Sockets for Full-Arch Restoration of Patients With Bruxism.

Science.gov (United States)

Mijiritsky, Eitan; Mortellaro, Carmen; Rudberg, Omri; Fahn, Miri; Basegmez, Cansu; Levin, Liran

2016-05-01

The aim of the present report was to describe the use of Botulinum toxin type A as preoperative treatment for immediately loaded dental implants placed in fresh extraction sockets for full-arch restoration of patients with bruxism. Patients with bruxism who were scheduled to receive immediately loaded full-arch implant supported fixed restorations were included in this retrospective clinical report. To reduce the occlusal forces applied in patients with bruxism, Botulinum toxin type A was introduced prior to the implant placement procedure. Patients were followed and implant survival as well as peri-implant bone level was assessed in each periodic follow-up visit. Adverse effects were also recorded. A control group with no use of Botulinum toxin was evaluated as well. A total of 26 patients (13 test and 13 control), with bruxism, aged 59.15 ± 11.43 years on average were included in this retrospective report and received immediately loaded dental implants placed in fresh extraction sockets for full-arch restoration. The test group treatment preceded by Botulinum toxin type A injection. Maxillary arches were supported by 8 to 10 implants while the mandibular arch was supported by 6 implants. All surgeries went uneventfully and no adverse effects were observed. The average follow-up time was 32.5 ± 10.4 months (range, 18-51). In the test group, no implant failures were recorded. One patient presented with 1 to 2 mm bone loss around 4 of the implants; the other implants presented with stable bone level. In the control group 1 patient lost 2 implants and another demonstrated 2 mm bone loss around 3 of the implants. The preoperative use of Botulinum toxin in patients with bruxism undergoing full-arch rehabilitation using immediately loaded dental implants placed in fresh extraction sockets seems to be a technique that deserves attention. Further long-term, large-scale randomized clinical trials will help to determine the additional benefit of this suggested

A survey of traditional Iranian food products for contamination with toxigenic Clostridium botulinum

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H.R. Tavakoli

Full Text Available Summary: This study aimed to determine the rate of Clostridium botulinum contamination in some traditional Iranian food products (cheese, kashk and salted fish and evaluate the efficacy of the mouse bioassay method in detection of C. botulinum toxins in these foods. A total of 131 samples (57 cheese, 11 kashk and 63 salted fish were collected and examined to determine the rate of contamination by C. botulinum. Standard monovalent anti-toxins were used to determine the types of toxin. C. botulinum bacteria were detected in 4.58% of the examined samples (1.52% of cheese and 3.06% of salted fish samples. While no contamination was detected in the kashk samples, C. botulinum types A and E were found to be dominant in cheese and salted fish samples, respectively. These results indicate—some traditional Iranian foods may be contaminated with different types of C. botulinum, and the consumption of these products, either raw or cooked, may contribute to food-borne intoxications. Keywords: Clostridium botulinum, Botulinum toxin, Traditional foods

Deeper than skin deep - The effect of botulinum toxin-A on emotion processing.

Science.gov (United States)

Baumeister, J-C; Papa, G; Foroni, F

2016-08-01

The effect of facial botulinum Toxin-A (BTX) injections on the processing of emotional stimuli was investigated. The hypothesis, that BTX would interfere with processing of slightly emotional stimuli and less with very emotional or neutral stimuli, was largely confirmed. BTX-users rated slightly emotional sentences and facial expressions, but not very emotional or neutral ones, as less emotional after the treatment. Furthermore, they became slower at categorizing slightly emotional facial expressions under time pressure. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adductor laryngeal breathing dystonia in NBIA treated with botulinum toxin-A

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Vinod Rai

2013-01-01

Full Text Available We report a rare case of neurodegeneration with brain iron accumulation (NBIA presented with episodic inspiratory stridor. A 10-year-old boy presented with 3-year history of gradually progressive spastic gait and generalized dystonia (involving all four limbs, neck, jaw, and speech. MRI brain showed "Eye of Tiger" sign. He recently developed severe inspiratory stridor associated with almost gasping respiration. Direct video laryngoscopy showed paradoxical vocal cord closure during inspiration. He was treated with EMG-guided botulinum toxin-A injection given into bilateral thyroarytenoid muscles, resulting in dramatic response with complete disappearance of the stridor within a week. The effect lasted 18 months.

GRIN: "GRoup versus INdividual physiotherapy following lower limb intra-muscular Botulinum Toxin-A injections for ambulant children with cerebral palsy: an assessor-masked randomised comparison trial": study protocol.

Science.gov (United States)

Thomas, Rachel E; Johnston, Leanne M; Boyd, Roslyn N; Sakzewski, Leanne; Kentish, Megan J

2014-02-07

Cerebral palsy is the most common cause of physical disability in childhood. Spasticity is a significant contributor to the secondary impairments impacting functional performance and participation. The most common lower limb spasticity management is focal intramuscular injections of Botulinum Toxin-Type A accompanied by individually-delivered (one on one) physiotherapy rehabilitation. With increasing emphasis on improving goal-directed functional activity and participation within a family-centred framework, it is timely to explore whether physiotherapy provided in a group could achieve comparable outcomes, encouraging providers to offer flexible models of physiotherapy delivery. This study aims to compare individual to group-based physiotherapy following intramuscular Botulinum Toxin-A injections to the lower limbs for ambulant children with cerebral palsy aged four to fourteen years. An assessor-masked, block randomised comparison trial will be conducted with random allocation to either group-based or individual physiotherapy. A sample size of 30 (15 in each study arm) will be recruited. Both groups will receive six hours of direct therapy following Botulinum Toxin-A injections in either an individual or group format with additional home programme activities (three exercises to be performed three times a week). Study groups will be compared at baseline (T1), then at 10 weeks (T2, efficacy) and 26 weeks (T3, retention) post Botulinum Toxin-A injections. Primary outcomes will be caregiver/s perception of and satisfaction with their child's occupational performance goals (Canadian Occupational Performance Measure) and quality of gait (Edinburgh Visual Gait Score) with a range of secondary outcomes across domains of the International Classification of Disability, Functioning and Health. This paper outlines the study protocol including theoretical basis, study hypotheses and outcome measures for this assessor-masked, randomised comparison trial comparing group versus

The European AntibotABE Framework Program and Its Update: Development of Innovative Botulinum Antibodies

Directory of Open Access Journals (Sweden)

Christine Rasetti-Escargueil

2017-10-01

Full Text Available The goal of the AntiBotABE Program was the development of recombinant antibodies that neutralize botulinum neurotoxins (BoNT A, B and E. These serotypes are lethal and responsible for most human botulinum cases. To improve therapeutic efficacy, the heavy and light chains (HC and LC of the three BoNT serotypes were targeted to achieve a synergistic effect (oligoclonal antibodies. For antibody isolation, macaques were immunized with the recombinant and non-toxic BoNT/A, B or E, HC or LC, followed by the generation of immune phage-display libraries. Antibodies were selected from these libraries against the holotoxin and further analyzed in in vitro and ex vivo assays. For each library, the best ex vivo neutralizing antibody fragments were germline-humanized and expressed as immunoglobulin G (IgGs. The IgGs were tested in vivo, in a standardized model of protection, and challenged with toxins obtained from collections of Clostridium strains. Protective antibody combinations against BoNT/A and BoNT/B were evidenced and for BoNT/E, the anti-LC antibody alone was found highly protective. The combination of these five antibodies as an oligoclonal antibody cocktail can be clinically and regulatorily developed while their high “humanness” predicts a high tolerance in humans.

Toxin production of non-proteolytic Cl. botulinum type B in radurized fish. Part of a coordinated programme on the wholesomeness of the process of food irradiation

International Nuclear Information System (INIS)

Suhadi, F.

1981-02-01

Toxin formation by proteolytic and nonproteolytic strains of C. botulinum type B in radurized raw fish and in radurized Pindang fish was investigated. In radurized Pindang fish samples, inoculation was done either before or after cooking. Radurization process with 2 and 3 kGy caused the extension of storage life of Rastrelliger sp., Euthynnus sp., and Scomberomorus sp. by factors of 2 and 2.5 at storage temperatures between 5 and 10 0 C. In general at 10.5 +- 0.3 0 C, no toxin was formed before the samples were spoiled both in irradiated and unirradiated samples. At 5.6 +- 0.5 0 C no toxin was formed until after the samples were spoiled. The earliest toxin formation in unirradiated Pindang samples stored at ambient temperature was detected after the samples were spoiled. In irradiated Pindang samples inoculated with C. botulinum spores after cooking and stored at ambient temperature the toxin formation was detected before the samples were spoiled. However, if the inoculation was done before the fish was processed into Pindang, the toxin was always detected after the samples were spoiled regardless of the irradiation dose, strain and inoculation level. As fish may be contaminated - if at all - with spores of C. botulinum in its raw state, processing of fish into Pindang and irradiation would not contribute to the health hazard concerning botulism even if the samples are stored at ambient temperature

Analysis of the mechanisms that underlie absorption of botulinum toxin by the inhalation route.

Science.gov (United States)

Al-Saleem, Fetweh H; Ancharski, Denise M; Joshi, Suresh G; Elias, M; Singh, Ajay; Nasser, Zidoon; Simpson, Lance L

2012-12-01

Botulinum toxin is a highly potent oral and inhalation poison, which means that the toxin must have an efficient mechanism for penetration of epithelial barriers. To date, three models for toxin passage across epithelial barriers have been proposed: (i) the toxin itself undergoes binding and transcytosis; (ii) an auxiliary protein, HA35, transports toxin from the apical to the basal side of epithelial cells; and (iii) an auxiliary protein, HA35, acts on the basal side of epithelial cells to disrupt tight junctions, and this permits paracellular flux of toxin. These models were evaluated by studying toxin absorption following inhalation exposure in mice. Three types of experiments were conducted. In the first, the potency of pure neurotoxin was compared with that of progenitor toxin complex, which contains HA35. The results showed that the rate and extent of toxin absorption, as well as the potency of absorbed toxin, did not depend upon, nor were they enhanced by, the presence of HA35. In the second type of experiment, the potencies of pure neurotoxin and progenitor toxin complex were compared in the absence or presence of antibodies on the apical side of epithelial cells. Antibodies directed against the neurotoxin protected against challenge, but antibodies against HA35 did not. In the final type of experiment, the potency of pure neurotoxin and toxin complex was compared in animals pretreated to deliver antibodies to the basal side of epithelial cells. Once again, antibodies directed against the neurotoxin provided resistance to challenge, but antibodies directed against HA35 did not. Taken collectively, the data indicate that the toxin by itself is capable of crossing epithelial barriers. The data do not support any hypothesis in which HA35 is essential for toxin penetration of epithelial barriers.

Electromyography-Guided Botulinum Toxin Injection Into the Cricothyroid Muscles in Bilateral Vocal Fold Abductor Paralysis

OpenAIRE

Sahin, Mustafa; Aydogdu, Ibrahim; Akyildiz, Serdar; Erdinc, Munevver; Ozturk, Kerem; Ogut, Fatih

2016-01-01

Objectives Bilateral vocal fold abductor paralysis (BVFAP) both deteriorates quality of life and may cause life-threatening respiratory problems. The aim of this study was to reduce respiratory symptoms in BVFAP patients using cricothyroid (CT) botulinum toxin (BTX) injection. Methods Before and 2 weeks and 4 months after bilateral BTX injection into the CT muscles under electromyography; alterations in respiratory, acoustic, aerodynamic and quality of life parameters were evaluated in BVFAP ...

Single-fiber electromyography analysis of botulinum toxin diffusion in patients with fatigue and pseudobotulism.

Science.gov (United States)

Ruet, Alexis; Durand, Marie Christine; Denys, Pierre; Lofaso, Frederic; Genet, François; Schnitzler, Alexis

2015-06-01

To characterize electromyographic abnormalities according to symptoms (asymptomatic, fatigue, pseudobotulism) reported 1 month after botulinum toxin injection. Retrospective, single-center study comparing single-fiber electromyography (SFEMG) in the extensor digitorum communis (EDC) or orbicularis oculi (OO) muscles. Hospital. Four groups of adults treated for spasticity or neurologic bladder hyperactivity (N=55): control group (asymptomatic patients: n=17), fatigue group (unusual fatigue with no weakness: n=15), pseudobotulism group (muscle weakness and/or visual disturbance: n=20), and botulism group (from intensive care unit of the same hospital: n=3). Not applicable. Mean jitter, percentage of pathologic fibers, and percentage of blocked fibers were compared between groups. SFEMG was abnormal for 17.6% of control patients and 75% of patients in the pseudobotulism group. There were no differences between the control and fatigue groups. Mean jitter, percentage of pathologic fibers, and percentage of blocked fibers of the EDC muscle were significantly higher in the pseudobotulism group than in the fatigue and control groups. There were no differences between groups for the OO muscle. The SFEMG results in the botulism group were qualitatively similar to those of the pseudobotulism group. SFEMG of the EDC muscle confirmed diffusion of the toxin into muscles distant from the injection site in the pseudobotulism group. SFEMG in the OO muscle is not useful for the diagnosis of diffusion. No major signs of diffusion of botulinum toxin type A were found away from the injection site in patients with fatigue but no motor weakness. Such fatigue may be related to other mechanisms. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Value of botulinum toxin injections preceding a comprehensive rehabilitation period for children with spastic cerebral palsy: A cost-effectiveness study

NARCIS (Netherlands)

F.C. Schasfoort (Fabiënne); A.J. Dallmeijer (Annet); R.F. Pangalila (Robert); C. Catsman (Coriene); H.J. Stam (Henk); J.G. Becher (Jules); E.W. Steyerberg (Ewout W.); S. Polinder (Suzanne); J.B.J. Bussmann (Hans); H.L.D. Horemans (Herwin); E.M. Sneekes (E.); Bolster, E. (Eline); Viola, I. (Irma); Beek, K. (Karlijn) van; J.M.A. Verheijden (Johannes)

2018-01-01

textabstractObjective: Despite the widespread use of botulinum toxin in ambulatory children with spastic cerebral palsy, its value prior to intensive physiotherapy with adjunctive casting/orthoses remains unclear. Design: A pragmatically designed, multi-centre trial, comparing the effectiveness of

Investigation of Clostridium botulinum group III's mobilome content.

Science.gov (United States)

Woudstra, Cédric; Le Maréchal, Caroline; Souillard, Rozenn; Anniballi, Fabrizio; Auricchio, Bruna; Bano, Luca; Bayon-Auboyer, Marie-Hélène; Koene, Miriam; Mermoud, Isabelle; Brito, Roseane B; Lobato, Francisco C F; Silva, Rodrigo O S; Dorner, Martin B; Fach, Patrick

2018-02-01

Clostridium botulinum group III is mainly responsible for botulism in animals. It could lead to high animal mortality rates and, therefore, represents a major environmental and economic concern. Strains of this group harbor the botulinum toxin locus on an unstable bacteriophage. Since the release of the first complete C. botulinum group III genome sequence (strain BKT015925), strains have been found to contain others mobile elements encoding for toxin components. In this study, seven assays targeting toxin genes present on the genetic mobile elements of C. botulinum group III were developed with the objective to better characterize C. botulinum group III strains. The investigation of 110 C. botulinum group III strains and 519 naturally contaminated samples collected during botulism outbreaks in Europe showed alpha-toxin and C2-I/C2-II markers to be systematically associated with type C/D bont-positive samples, which may indicate an important role of these elements in the pathogenicity mechanisms. On the contrary, bont type D/C strains and the related positive samples appeared to contain almost none of the markers tested. Interestingly, 31 bont-negative samples collected on farms after a botulism outbreak revealed to be positive for some of the genetic mobile elements tested. This suggests loss of the bont phage, either in farm environment after the outbreak or during laboratory handling. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Medical Research and Evaluation Facility (MREF) and Studies Supporting the Medical Chemical Defense Program: Task 95-39: Methods Development and Validation of Two Mouse Bioassays for Use in Quantifying Botulinum Toxins (A, B, C, D and E) and Toxin Antibody Titers

National Research Council Canada - National Science Library

Olson, Carl

1997-01-01

Ths task was conducted for the U.S. Army Medical Materiel Development Activity (USAMMDA) to validate two mouse bioassays for quantify botulinum toxin potency and neutralizing antibodies to botulimun toxins...

A Single-blind, Split-face, Randomized, Pilot Study Comparing the Effects of Intradermal and Intramuscular Injection of Two Commercially Available Botulinum Toxin A Formulas to Reduce Signs of Facial Aging

Science.gov (United States)

Sapra, Priya; Sapra, Sheetal; Khanna, Julie; Mraud, Kelli; Bonadonna, Jennifer

2017-01-01

Objective: To examine the effectiveness of intradermal botulinum toxin type A injection in improving skin texture and midface lift while reducing pore size and sebum production, as well as investigate the differences in effectiveness between onabotulinumtoxinA and abobotulinumtoxinA using intradermal and intramuscular injection methods. Design: A 16-week, single-blind, split-face, randomized study. Each patient served as their own control, receiving onabotulinumtoxinA and abobotulinumtoxinA randomized to either the left or right side of the face. Patients received intradermal botulinum toxin type A injections at Week 0 and intramuscular botulinum toxin type A injections at Week 2. Participants: Ten women aged 35 to 65 years who exhibited static rhytids in the glabellar and periorbital area. Measurements: The primary endpoint was efficacy of split-face treatment of intradermal and intramuscular onabotulinumtoxinA and abobotulinumtoxinA as assessed by a blinded evaluator using baseline and post-treatment photographs. The secondary endpoints included safety as assessed by adverse events and patient satisfaction measured by questionnaires completed at baseline and post-treatment. Results: Intradermal injection of botulinum toxin type A led to a statistically significant improvement in skin texture (p=0.004) while also resulting in mild midface lift (p=0.024), but did not provide a significant reduction of pore size and sebum production. There was no statistically significant difference between onabotulinumtoxinA and abobotulinumtoxinA when injected intradermally or intramuscularly. Conclusion: Intradermal injection of botulinum toxin type A appears to be a safe and effective therapy that provides an improvement in facial skin texture and midface lift. Registry: clinicaltrials.gov (ID#: NCT02907268). PMID:28367260

Botulinum toxin type A for the treatment of sialorrhoea in amyotrophic lateral sclerosis: a clinical and neurophysiological study.

Science.gov (United States)

Gilio, Francesca; Iacovelli, Elisa; Frasca, Vittorio; Gabriele, Maria; Giacomelli, Elena; Picchiori, Floriana; Soldo, Pietro; Cipriani, Anna Maria; Ruoppolo, Giovanni; Inghilleri, Maurizio

2010-08-01

Botulinum toxin type A (BoNT/A) has been proposed as an alternative treatment for sialorrhoea in patients with amyotrophic lateral sclerosis (ALS). In an open-label prospective study, BoNT/A was injected into the parotid glands bilaterally using anatomic landmarks in 26 ALS patients with bulbar symptoms. Two weeks after injection the severity of sialorrhoea and the related disability were evaluated subjectively and objectively. A group of healthy subjects acted as controls for saliva production. Patients also underwent electrophysiological tests to evaluate possible toxin effects in the nearby non-injected muscles by comparing the amplitude of compound motor action potentials (cMAPs) elicited by electrical stimulation and recorded from the orbicularis oculi and masseter muscles. After BoNT/A injections, of the 26 patients treated, 23 reported that the severity of sialorrhoea improved and the disabling symptoms diminished. Cotton roll weight also decreased after BoNT/A injection, suggesting a reduction in saliva production. Two patients complained of dry mouth. BoNT/A injection left the cMAP amplitude unchanged, suggesting that botulinum toxin does not significantly affect the non-injected facial and masticatory muscles. In conclusion, intraparotid anatomically-guided BoNT/A injection is an effective, easy, and safe treatment for sialorrhoea in patients with bulbar symptoms related to ALS.

Botulinum toxin in myotonia congenita: it does not help against rigidity and pain.

Science.gov (United States)

Dressler, Dirk; Adib Saberi, Fereshte

2014-05-01

Botulinum toxin (BT) is a potent local muscle relaxant with analgetic properties. Myotonia congenita (MC) is a genetic disorder producing muscle rigidity and pain. BT injected into the trapezius produced mild paresis, but no effect on rigidity and pain. There were no signs of systemic effects. Lack of BT efficacy on MC rigidity confirms its origin from muscle membrane dysfunction rather than from inappropriate neuromuscular activation. Lack of BT efficacy on pain could be caused by lack of anti-rigidity effect. It could also be due to separate non-muscular pain mechanisms unresponsive to BT.

Botox facial slimming/facial sculpting: the role of botulinum toxin-A in the treatment of hypertrophic masseteric muscle and parotid enlargement to narrow the lower facial width.

Science.gov (United States)

Wu, Woffles T L

2010-02-01

Botulinum toxin A is a highly efficacious and cost-effective, nonsurgical option for reducing the width and shape of the lower face and jawline. The results can vary from the subtlest thinning of the face to an extremely thin, cachectic appearance. Many nuances can be achieved. The administration is simple, and the process takes barely 5 minutes in an office setting. Botulinum toxin A can also be effectively used to reduce the bulk of an enlarged parotid gland without affecting saliva production. Copyright 2010. Published by Elsevier Inc.

The utility of EMG interference pattern analysis in botulinum toxin treatment of torticollis: A randomised, controlled and blinded study

DEFF Research Database (Denmark)

Werdelin, L; Dalager, T; Fuglsang-Frederiksen, Anders

2011-01-01

OBJECTIVE: The significance of electromyography (EMG) guidance in botulinum toxin (BT) treatment has been much debated. The aim of this study was to evaluate if EMG guidance in the treatment of torticollis in BT-naive patients had a better outcome than treatment after clinical evaluation alone...

Bioterrorism: toxins as weapons.

Science.gov (United States)

Anderson, Peter D

2012-04-01

The potential for biological weapons to be used in terrorism is a real possibility. Biological weapons include infectious agents and toxins. Toxins are poisons produced by living organisms. Toxins relevant to bioterrorism include ricin, botulinum, Clostridium perfrigens epsilson toxin, conotoxins, shigatoxins, saxitoxins, tetrodotoxins, mycotoxins, and nicotine. Toxins have properties of biological and chemical weapons. Unlike pathogens, toxins do not produce an infection. Ricin causes multiorgan toxicity by blocking protein synthesis. Botulinum blocks acetylcholine in the peripheral nervous system leading to muscle paralysis. Epsilon toxin damages cell membranes. Conotoxins block potassium and sodium channels in neurons. Shigatoxins inhibit protein synthesis and induce apoptosis. Saxitoxin and tetrodotoxin inhibit sodium channels in neurons. Mycotoxins include aflatoxins and trichothecenes. Aflatoxins are carcinogens. Trichothecenes inhibit protein and nucleic acid synthesis. Nicotine produces numerous nicotinic effects in the nervous system.

Complete subunit structure of the Clostridium botulinum type D toxin complex via intermediate assembly with nontoxic components.

Science.gov (United States)

Mutoh, Shingo; Kouguchi, Hirokazu; Sagane, Yoshimasa; Suzuki, Tomonori; Hasegawa, Kimiko; Watanabe, Toshihiro; Ohyama, Tohru

2003-09-23

Clostridium botulinum serotype D strains usually produce two types of stable toxin complex (TC), namely, the 300 kDa M (M-TC) and the 660 kDa L (L-TC) toxin complexes. We previously proposed assembly pathways for both TCs [Kouguchi, H., et al. (2002) J. Biol. Chem. 277, 2650-2656]: M-TC is composed by association of neurotoxin (NT) and nontoxic nonhemagglutinin (NTNHA); conjugation of M-TC with three auxiliary types of hemagglutinin subcomponents (HA-33, HA-17, and HA-70) leads to the formation of L-TC. In this study, we found three TC species, 410, 540, and 610 kDa TC species, in the culture supernatant of type D strain 4947. The 540 and 610 kDa TC species displayed banding patterns on SDS-PAGE similar to that of L-TC but with less staining intensity of the HA-33 and HA-17 bands than those of L-TC, indicating that these are intermediate species in the pathway to L-TC assembly. In contrast, the 410 kDa TC species consisted of M-TC and two molecules of HA-70. All of the TC species, except L-TC, demonstrated no hemagglutination activity. When the intermediate TC species were mixed with an isolated HA-33/17 complex, every TC species converted to 650 kDa L-TC with full hemagglutination activity and had the same molecular composition of L-TC. On the basis of titration analysis with the HA-33/17 complex, the stoichiometry of the HA-33/17 complex molecules in the L-TC, 610 kDa, and 540 kDa TC species was estimated as 4, 3, and 2, respectively. In conclusion, the complete subunit composition of mature L-TC is deduced to be a dodecamer assembled by a single NT, a single NTNHA, two HA-70, four HA-33, and four HA-17 molecules.

Botulinum toxin for treating muscular temporomandibular disorders: a systematic review

Directory of Open Access Journals (Sweden)

Eduardo Machado

2012-12-01

Full Text Available OBJECTIVE: This study, through a systematic literature review, aims to analyze the effectiveness of Botulinum Toxin as a treatment for masticatory myofascial pain and muscles temporomandibular disorders (TMD. METHODS: Survey in research bases: MEDLINE, Cochrane, EMBASE, Pubmed, Lilacs and BBO, between the years of 1966 and April 2011, with focus in randomized or quasi-randomized controlled clinical trials, blind or double-blind. RESULTS: After applying the inclusion criteria, 4 articles comprised the final sample: 3 were double-blind randomized controlled clinical trials and 1 was single-blind randomized controlled clinical trial. CONCLUSIONS: According to the literature, there is lack of evidence about the real effectiveness of botulinum toxin in the treatment of masticatory myofascial pain and muscular TMD. Thus, further randomized controlled clinical trials, with representative samples and longer follow-up time, to assess the real effectiveness of the technique are needed.OBJETIVO: este trabalho, por meio de uma revisão sistemática da literatura, teve como objetivo analisar a efetividade da toxina botulínica como tratamento para dor miofascial mastigatória e disfunções temporomandibulares (DTM musculares. MÉTODOS: pesquisa nas bases de dados Medline, Cochrane, Embase, Pubmed, Lilacs e BBO, no período entre 1966 e abril de 2011, com enfoque em estudos clínicos controlados randomizados ou quase-randomizados, cegos ou duplo-cegos. RESULTADOS: após a aplicação dos critérios de inclusão, chegou-se a 4 artigos, sendo que 3 eram estudos clínicos controlados randomizados duplo-cego e 1 era estudo clínico controlado randomizado simples-cego. CONCLUSÕES: pela análise da literatura, verificou-se um número reduzido de evidências significativas sobre a real efetividade da toxina botulínica no tratamento da dor miofascial e de DTM musculares. Assim, são necessários novos estudos clínicos controlados randomizados, com amostras

Botulinum toxin type-A in therapy of patients with anismus.

Science.gov (United States)

Ron, Y; Avni, Y; Lukovetski, A; Wardi, J; Geva, D; Birkenfeld, S; Halpern, Z

2001-12-01

Anismus is a common cause of constipation and outlet obstruction. Standard therapy with laxatives or biofeedback has conflicting results. Surgical treatment gives poor results and has practically been abandoned. This study was designed to evaluate the efficacy of botulinum toxin type-A (Botox) injection to the puborectalis muscle in patients with anismus. Twenty-five patients (15 females; mean age, 23.2) with history of constipation and symptoms of outlet obstruction underwent anorectal perfusion manometry and video-proctography. All patients were found to have a nonrelaxing puborectalis muscle on both modalities. All have been unable to expel a rectal balloon. Each patient who participated in the study was randomly assigned to undergo local injection of Botox--10 units to each side of the puborectalis or 20 units to the posterior aspect of this muscle. Eight patients underwent further injections1-5 every 3 months in accordance with previous results. Follow-up was conducted 1, 4, 12, and 24 weeks after injection. Straining, anorectal pain, and overall satisfaction were assessed on a visual analog scale. Weekly evacuation, fecal incontinence, and complications were recorded. At the weekly meeting, each patient underwent anorectal manometry with a balloon expulsion test. Manometric relaxation was achieved after the first injection in 18 patients (75 percent). Once relaxation was achieved, it lasted throughout the follow-up. Nine patients (37.5 percent) expelled the rectal balloon after the first injection. Seven of 16 patients who failed the first injection had an additional one. In 2 patients it was successful (28.6 percent). Symptom improvement of 29.2 percent in straining index was recorded during follow-up. In 3 patients (12.5 percent) pain developed after injection. No other complications were observed. Overall satisfaction with Botox injection results was observed in 58.3 percent. Botox injection to the puborectalis muscle has been found to have a limited

Structural insight into exosite binding and discovery of novel exosite inhibitors of botulinum neurotoxin serotype A through in silico screening

Science.gov (United States)

Hu, Xin; Legler, Patricia M.; Southall, Noel; Maloney, David J.; Simeonov, Anton; Jadhav, Ajit

2014-07-01

Botulinum neurotoxin serotype A (BoNT/A) is the most lethal toxin among the Tier 1 Select Agents. Development of potent and selective small molecule inhibitors against BoNT/A zinc metalloprotease remains a challenging problem due to its exceptionally large substrate binding surface and conformational plasticity. The exosites of the catalytic domain of BoNT/A are intriguing alternative sites for small molecule intervention, but their suitability for inhibitor design remains largely unexplored. In this study, we employed two recently identified exosite inhibitors, D-chicoric acid and lomofungin, to probe the structural features of the exosites and molecular mechanisms of synergistic inhibition. The results showed that D-chicoric acid favors binding at the α-exosite, whereas lomofungin preferentially binds at the β-exosite by mimicking the substrate β-sheet binding interaction. Molecular dynamics simulations and binding interaction analysis of the exosite inhibitors with BoNT/A revealed key elements and hotspots that likely contribute to the inhibitor binding and synergistic inhibition. Finally, we performed database virtual screening for novel inhibitors of BoNT/A targeting the exosites. Hits C1 and C2 showed non-competitive inhibition and likely target the α- and β-exosites, respectively. The identified exosite inhibitors may provide novel candidates for structure-based development of therapeutics against BoNT/A intoxication.

Patient Perceived Benefit in Facial Aesthetic Procedures: FACE-Q as a Tool to Study Botulinum Toxin Injection Outcomes.

Science.gov (United States)

Chang, Brian L; Wilson, Anthony J; Taglienti, Anthony J; Chang, Catherine S; Folsom, Nancy; Percec, Ivona

2016-07-01

There are numerous methods of assessing patient satisfaction with botulinum toxin type A neuromodulation of the glabellar rhytids. As the use of aesthetic neuromodulation increases both in breadth and number of procedures, there is a need for more comprehensive tools to evaluate patient-reported outcomes. The FACE-Q is a recently validated patient-reported outcome instrument that can be used to measure patient perceptions of botulinum toxin type A neuromodulation. This study used the FACE-Q to assess patient satisfaction following botulinum toxin type A neuromodulation of the glabellar rhytids. 57 female patients completed the FACE-Q, a survey that evaluates patients' satisfaction with their facial appearance. After this baseline survey, the patients received injections of one of onabotulinumtoxinA (Botox, Allergan, Dublin, Ireland), abobotulinumtoxinA (Dysport, Galderma, Lausanne, Switzerland), or incobotulinumtoxinA (Xeomin, Merz Pharmaceuticals, Frankfurt am Main, Germany) in the glabella. Two weeks post-injection, the patients completed the FACE-Q again. The percentage changes in patient responses were tabulated to determine how neuromodulation affects patient satisfaction with their facial appearance. The percentage changes for each of the neurotoxin groups were compared to determine if patient satisfaction with neuromodulation varies with the type of neurotoxin. Patient satisfaction with their overall facial appearance increased by 28% following neuromodulation. Patients stated that they believe they look an average of 5.6 years younger post-neuromodulation. There were no significant differences among the treatment groups. The FACE-Q demonstrates that patients are more satisfied by their overall facial appearance and age appearance following neuromodulation of their glabellar rhytids. Patients are equally satisfied with the improvement of their facial appearance regardless of which neurotoxin they received. LEVEL OF EVIDENCE 2: Therapeutic. © 2016 The

Minimal Essential Domains Specifying Toxicity of the Light Chains of Tetanus Toxin and Botulinum Neurotoxin Type A

NARCIS (Netherlands)

Kurazono, Hisao; Mochida, Sumiko; Binz, Thomas; Eisel, Ulrich; Quanz, Martin; Grebenstein, Oliver; Wernars, Karel; Poulain, Bernard; Tauc, Ladislav; Niemann, Heiner

1992-01-01

To define conserved domains within the light (L) chains of clostridial neurotoxins, we determined the sequence of botulinum neurotoxin type B (BoNT/B) and aligned it with those of tetanus toxin (TeTx) and BoNT/A, BoNT/Cl, BoNT/D, and BoNT/E. The L chains of BoNT/B and TeTx share 51.6% identical

Epidemiologic Overview of Synkinesis in 353 Patients with Longstanding Facial Paralysis under Treatment with Botulinum Toxin for 11 Years.

Science.gov (United States)

Salles, Alessandra Grassi; da Costa, Eduardo Fernandes; Ferreira, Marcus Castro; Remigio, Adelina Fatima do Nascimento; Moraes, Luciana Borsoi; Gemperli, Rolf

2015-12-01

Patients with longstanding facial paralysis often exhibit synkinesis. Few reports describe the prevalence and factors related to the development of synkinesis after facial paralysis. Botulinum toxin type A injection is an important adjunct treatment for facial paralysis-induced asymmetry and synkinesis. The authors assessed the clinical and epidemiologic characteristics of patients with sequelae of facial paralysis treated with botulinum toxin type A injections to evaluate the prevalence of synkinesis and related factors. A total of 353 patients (age, 4 to 84 years; 245 female patients) with longstanding facial paralysis underwent 2312 botulinum toxin type A injections during an 11-year follow-up. Doses used over the years, previous treatments (electrical stimulation, operations), and how they correlated to postparalysis and postreanimation synkinesis were analyzed. There was a significant association between cause and surgery. Most patients with facial paralysis caused by a congenital defect, trauma, or a tumor underwent reanimation. There were no sex- or synkinesis-related differences in the doses used, but the doses were higher in the reanimation group than in the no-surgery group. Synkinesis was found in 196 patients; 148 (41.9 percent) presented with postparalysis synkinesis (oro-ocular, oculo-oral) and 58 (16.4 percent) presented with postreanimation synkinesis. Ten patients presented with both types. This study determined the high prevalence (55.5 percent) of synkinesis in patients with longstanding facial paralysis. Postparalysis synkinesis was positively associated with infectious and idiopathic causes, electrical stimulation, facial nerve decompression, and no requirement for surgery. Postreanimation synkinesis was present in 28.2 percent of reanimated patients and was significantly associated with microsurgical flaps, transfacial nerve grafting, masseteric-facial anastomosis, and temporalis muscle transfers.

Alternative Approach to Traumatic Stensen’s Duct Injuries Accompanied by Glandular Involvement: Botulinum Toxin Injection to the Gland in Conjunction with Microsurgical Repair of the Duct in an Acute Setting

OpenAIRE

Mert Çalış; Zeynep Öz; Hakan Uzun; Burçe Özgen; Alp Çetin3; Ali Emre Aksu

2017-01-01

Objective: The aim of this study was to evaluate the long-term results of a simultaneous application of botulinum toxin to the parotid gland in conjunction with the microsurgical repair of the duct in an acute setting and to encourage using botulinum toxin as a first-line option to prevent future complications associated with glandular involvement. Material and Methods: Three patients who were referred to the Plastic Surgery Clinic by the emergency room of the Hacettepe University Hospita...

Recommended Immunological Strategies to Screen for Botulinum Neurotoxin-Containing Samples

Directory of Open Access Journals (Sweden)

Stéphanie Simon

2015-11-01

Full Text Available Botulinum neurotoxins (BoNTs cause the life-threatening neurological illness botulism in humans and animals and are divided into seven serotypes (BoNT/A–G, of which serotypes A, B, E, and F cause the disease in humans. BoNTs are classified as “category A” bioterrorism threat agents and are relevant in the context of the Biological Weapons Convention. An international proficiency test (PT was conducted to evaluate detection, quantification and discrimination capabilities of 23 expert laboratories from the health, food and security areas. Here we describe three immunological strategies that proved to be successful for the detection and quantification of BoNT/A, B, and E considering the restricted sample volume (1 mL distributed. To analyze the samples qualitatively and quantitatively, the first strategy was based on sensitive immunoenzymatic and immunochromatographic assays for fast qualitative and quantitative analyses. In the second approach, a bead-based suspension array was used for screening followed by conventional ELISA for quantification. In the third approach, an ELISA plate format assay was used for serotype specific immunodetection of BoNT-cleaved substrates, detecting the activity of the light chain, rather than the toxin protein. The results provide guidance for further steps in quality assurance and highlight problems to address in the future.

Recommended Immunological Strategies to Screen for Botulinum Neurotoxin-Containing Samples.

Science.gov (United States)

Simon, Stéphanie; Fiebig, Uwe; Liu, Yvonne; Tierney, Rob; Dano, Julie; Worbs, Sylvia; Endermann, Tanja; Nevers, Marie-Claire; Volland, Hervé; Sesardic, Dorothea; Dorner, Martin B

2015-11-26

Botulinum neurotoxins (BoNTs) cause the life-threatening neurological illness botulism in humans and animals and are divided into seven serotypes (BoNT/A-G), of which serotypes A, B, E, and F cause the disease in humans. BoNTs are classified as "category A" bioterrorism threat agents and are relevant in the context of the Biological Weapons Convention. An international proficiency test (PT) was conducted to evaluate detection, quantification and discrimination capabilities of 23 expert laboratories from the health, food and security areas. Here we describe three immunological strategies that proved to be successful for the detection and quantification of BoNT/A, B, and E considering the restricted sample volume (1 mL) distributed. To analyze the samples qualitatively and quantitatively, the first strategy was based on sensitive immunoenzymatic and immunochromatographic assays for fast qualitative and quantitative analyses. In the second approach, a bead-based suspension array was used for screening followed by conventional ELISA for quantification. In the third approach, an ELISA plate format assay was used for serotype specific immunodetection of BoNT-cleaved substrates, detecting the activity of the light chain, rather than the toxin protein. The results provide guidance for further steps in quality assurance and highlight problems to address in the future.

Isolation and functional characterization of the novel Clostridium botulinum neurotoxin A8 subtype.

Science.gov (United States)

Kull, Skadi; Schulz, K Melanie; Weisemann, Jasmin; Kirchner, Sebastian; Schreiber, Tanja; Bollenbach, Alexander; Dabrowski, P Wojtek; Nitsche, Andreas; Kalb, Suzanne R; Dorner, Martin B; Barr, John R; Rummel, Andreas; Dorner, Brigitte G

2015-01-01

Botulism is a severe neurological disease caused by the complex family of botulinum neurotoxins (BoNT). Based on the different serotypes known today, a classification of serotype variants termed subtypes has been proposed according to sequence diversity and immunological properties. However, the relevance of BoNT subtypes is currently not well understood. Here we describe the isolation of a novel Clostridium botulinum strain from a food-borne botulism outbreak near Chemnitz, Germany. Comparison of its botulinum neurotoxin gene sequence with published sequences identified it to be a novel subtype within the BoNT/A serotype designated BoNT/A8. The neurotoxin gene is located within an ha-orfX+ cluster and showed highest homology to BoNT/A1, A2, A5, and A6. Unexpectedly, we found an arginine insertion located in the HC domain of the heavy chain, which is unique compared to all other BoNT/A subtypes known so far. Functional characterization revealed that the binding characteristics to its main neuronal protein receptor SV2C seemed unaffected, whereas binding to membrane-incorporated gangliosides was reduced in comparison to BoNT/A1. Moreover, we found significantly lower enzymatic activity of the natural, full-length neurotoxin and the recombinant light chain of BoNT/A8 compared to BoNT/A1 in different endopeptidase assays. Both reduced ganglioside binding and enzymatic activity may contribute to the considerably lower biological activity of BoNT/A8 as measured in a mouse phrenic nerve hemidiaphragm assay. Despite its reduced activity the novel BoNT/A8 subtype caused severe botulism in a 63-year-old male. To our knowledge, this is the first description and a comprehensive characterization of a novel BoNT/A subtype which combines genetic information on the neurotoxin gene cluster with an in-depth functional analysis using different technical approaches. Our results show that subtyping of BoNT is highly relevant and that understanding of the detailed toxin function might

Fatal Clostridium botulinum toxicosis in eleven Holstein cattle fed round bale barley haylage.

Science.gov (United States)

Kelch, W J; Kerr, L A; Pringle, J K; Rohrbach, B W; Whitlock, R H

2000-09-01

Twenty-two lactating Holstein cattle in Tennessee had clinical signs of intoxication with preformed Clostridium botulinum toxin. These signs included weakness, paralysis of the tongue and chest muscles, abdominal breathing, and, in 11 of the 22 cows, death. Differential diagnoses included hypocalcemia, hypomagnesemia, carbohydrate overload, and several toxicoses including mycotoxin, lead, nitrate, organophosphate, atropine or atropine-like alkaloid, and botulism. A diagnosis of botulism by the ingestion of preformed C. botulinum type B toxin was made by eliminating these other diseases, by finding C. botulinum type B spores in 3 bales of round bale barley haylage fed to these cattle, and by isolating preformed type B toxin from 1 of the 3 bales. Confirmation of the toxin type was made by demonstrating mouse lethality by intraperitoneal injection of specimen extracts with neutralization by C. botulinum type B antitoxin. The haylage, harvested green and encased in black plastic bags to facilitate fermentation, was presumably contaminated by the botulinum toxin when fermentation failed to produce enough acid to lower the pH to 4.5, the pH below which C. botulinum growth is inhibited. Farmers and ranchers who use round hay balers to produce haylage should be alert to this potential problem.

The Use of Botulinum Toxin for the Treatment of Muscle Spasticity in the First 2 Years of Life

Science.gov (United States)

Bakheit, Abdel Magid

2010-01-01

Although there are sound theoretical reasons for the use of botulinum toxin (Btx) as early as possible in the management of severe childhood muscle spasticity, the experience with its safety in children younger than 2 years of age is limited and information about its possible effects on the development and maturation of the human motor system…

Botulinum Toxin Type A as a Therapeutic Agent against Headache and Related Disorders

Science.gov (United States)

Luvisetto, Siro; Gazerani, Parisa; Cianchetti, Carlo; Pavone, Flaminia

2015-01-01

Botulinum neurotoxin A (BoNT/A) is a toxin produced by the naturally-occurring Clostridium botulinum that causes botulism. The potential of BoNT/A as a useful medical intervention was discovered by scientists developing a vaccine to protect against botulism. They found that, when injected into a muscle, BoNT/A causes a flaccid paralysis. Following this discovery, BoNT/A has been used for many years in the treatment of conditions of pathological muscle hyperactivity, like dystonias and spasticities. In parallel, the toxin has become a “glamour” drug due to its power to ward off facial wrinkles, particularly frontal, due to the activity of the mimic muscles. After the discovery that the drug also appeared to have a preventive effect on headache, scientists spent many efforts to study the potentially-therapeutic action of BoNT/A against pain. BoNT/A is effective at reducing pain in a number of disease states, including cervical dystonia, neuropathic pain, lower back pain, spasticity, myofascial pain and bladder pain. In 2010, regulatory approval for the treatment of chronic migraine with BoNT/A was given, notwithstanding the fact that the mechanism of action is still not completely elucidated. In the present review, we summarize experimental evidence that may help to clarify the mechanisms of action of BoNT/A in relation to the alleviation of headache pain, with particular emphasis on preclinical studies, both in animals and humans. Moreover, we summarize the latest clinical trials that show evidence on headache conditions that may obtain benefits from therapy with BoNT/A. PMID:26404377

Sugar-binding sites of the HA1 subcomponent of Clostridium botulinum type C progenitor toxin.

Science.gov (United States)

Nakamura, Toshio; Tonozuka, Takashi; Ide, Azusa; Yuzawa, Takayuki; Oguma, Keiji; Nishikawa, Atsushi

2008-02-22

Clostridium botulinum type C 16S progenitor toxin contains a hemagglutinin (HA) subcomponent, designated HA1, which appears to play an important role in the effective internalization of the toxin in gastrointestinal epithelial cells and in creating a broad specificity for the oligosaccharide structure that corresponds to various targets. In this study, using the recombinant protein fused to glutathione S-transferase, we investigated the binding specificity of the HA1 subcomponent to sugars and estimated the binding sites of HA1 based on X-ray crystallography and soaking experiments using various sugars. N-Acetylneuraminic acid, N-acetylgalactosamine, and galactose effectively inhibited the binding that occurs between glutathione S-transferase-HA1 and mucins, whereas N-acetylglucosamine and glucose did not inhibit it. The crystal structures of HA1 complex with N-acetylneuraminic acid, N-acetylgalactosamine, and galactose were also determined. There are two sugar-binding sites, sites I and II. Site I corresponds to the electron densities noted for all sugars and is located at the C-terminal beta-trefoil domain, while site II corresponds to the electron densities noted only for galactose. An aromatic amino acid residue, Trp176, at site I has a stacking interaction with the hexose ring of the sugars. On the other hand, there is no aromatic residue at site II; thus, the interaction with galactose seems to be poor. The double mutant W176A at site I and D271F at site II has no avidity for N-acetylneuraminic acid but has avidity for galactose. In this report, the binding specificity of botulinum C16S toxin HA1 to various sugars is demonstrated based on its structural features.

Molecular scaffold reorganization at the transmitter release site with vesicle exocytosis or botulinum toxin C1.

Science.gov (United States)

Stanley, Elise F; Reese, Tom S; Wang, Gary Z

2003-10-01

Neurotransmitter release sites at the freeze-fractured frog neuromuscular junction are composed of inner and outer paired rows of large membrane particles, the putative calcium channels, anchored by the ribs of an underlying protein scaffold. We analysed the locations of the release site particles as a reflection of the scaffold structure, comparing particle distributions in secreting terminals with those where secretion was blocked with botulinum toxin A, which cleaves a small segment off SNAP-25, or botulinum toxin C1, which cleaves the cytoplasmic domain of syntaxin. In the idle terminal the inner and outer paired rows were located approximately 25 and approximately 44 nm, respectively, from the release site midline. However, adjacent to vesicular fusion sites both particle rows were displaced towards the midline by approximately 25%. The intervals between the particles along each row were examined by a nearest-neighbour approach. In control terminals the peak interval along the inner row was approximately 17 nm, consistent with previous reports and the spacing of the scaffold ribs. While the average distance between particles in the outer row was also approximately 17 nm, a detailed analysis revealed short 'linear clusters' with a approximately 14 nm interval. These clusters were enriched at vesicle fusion sites, suggesting an association with the docking sites, and were eliminated by botulinum C1, but not A. Our findings suggest, first, that the release site scaffold ribs undergo a predictable, and possibly active, shortening during exocytosis and, second, that at the vesicle docking site syntaxin plays a role in the cross-linking of the rib tips to form the vesicle docking sites.

Factors affecting growth and toxin production by Clostridium botulinum type E on irradiated (0.3 Mrad) chicken skins

International Nuclear Information System (INIS)

Firstenberg-Eden, R.; Rowley, D.B.; Shattuck, G.E.

1982-01-01

A model system (chicken skins with chicken exudate) was used to determine if Clostridium botulinum type E (Beluga) spores, stressed by low dose irradiation, would develop and produce toxin at abuse temperatures of 10 and 30 0 C in the absence of characteristic spoilage. Unstressed spores germinated, multiplied, and produced toxin on vacuum-packed chicken skins, stored at either 30 or 10 0 C. Cell numbers increased faster and toxin was evident sooner at 30 0 C than at 10 0 C. At 30 0 C, growth occurred and toxin was produced more slowly when samples were incubated aerobically than anaerobically. When samples were incubated aerobically at 10 0 C, no toxin was detected within a test period of 14 days. An irradiation dose of 0.3 Mrad at 5 0 C reduced a spore population on vacuum-sealed chicken skins by about 90%. The surviving population produced toxin at 30 0 C under either aerobic or anaerobic conditions, at 10 0 C no toxin was detected even on skins incubated anaerobically. Under the worst conditions (30 0 C, vacuum packed) toxin was not detected prior to characteristic spoilage caused by the natural flora surviving 0.3 Mrad

Botulinum Toxin Type a Injection, Followed by Home-Based Functional Training for Upper Limb Hemiparesis after Stroke

Science.gov (United States)

Takekawa, Toru; Kakuda, Wataru; Taguchi, Kensuke; Ishikawa, Atsushi; Sase, Yousuke; Abo, Masahiro

2012-01-01

Botulinum toxin type A (BoNT-A) has been reported to be an effective treatment for limb spasticity after stroke. However, the reduction in the spasticity after BoNT-A injection alone does not ensure an improvement in the active motor function of the affected limb. The aim of this study was to clarify the clinical effects of a BoNT-A injection,…

Reconstituting botulinum toxin drugs: shaking, stirring or what?

Science.gov (United States)

Dressler, Dirk; Bigalke, Hans

2016-05-01

Most botulinum toxin (BT) drugs are stored as powders which need to be reconstituted with normal saline before clinical use. As botulinum neurotoxin (BNT), the therapeutically active ingredient, is a large double-stranded protein the process of reconstitution should be performed with special attention to mechanical stress applied. We wanted to test the mechanical stability of BNT during the reconstitution process. For this, 100 MU onabotulinumtoxinA (Botox(®), Irvine, CA, USA) was reconstituted with 2.0 ml of NaCl/H2O. Gentle reconstitution (GR) was performed with a 5 ml syringe, a 0.90 × 70 mm injection needle, one cycle of injection-aspiration-injection and two gentle shakes of the vial. Aggressive reconstitution (AR) was performed with a 5 ml syringe, a 0.40 × 40 mm injection needle, ten injection-aspiration-injection cycles and 30 s of continuous shaking of the vial. AR increased the time to paralysis in the mouse hemidiaphragm assay (HDA) from 72.0 ± 4.6 to 106.0 ± 16.0 min (*p = 0.002, two-tailed t test after Kolmogorov-Smirnova test with Lilliefors correction for normal distribution). Construction of a calibration curve revealed that the increase in the time to paralysis was correlated with a loss of potency of from 100 to 58 MU (-42 %). BT users should use large diameter injection needles for reconstitution, apply two or three injection-aspiration-injection cycles and, maybe, shake the vials a few times to rinse the entire glass wall. Aggressive reconstitution with small diameter needles, prolonged injection-aspiration-injection and violent shaking should be avoided.

Botulinum toxin treatment for limb spasticity in childhood cerebral palsy

Directory of Open Access Journals (Sweden)

Vito ePavone

2016-02-01

Full Text Available CP is the most common cause of chronic disability in childhood occurring in 2 to 2.5/1000 births. It is a severe disorder and a significant number of patients present cognitive delay and difficulty in walking. The use of botulinum toxin (BTX has become a popular treatment for CP especially for spastic and dystonic muscles while avoiding deformity and pain. Moreover, the combination of physiotherapy, casting, orthotics and injection of BTX may delay or decrease the need for surgical intervention while reserving single-event, multi-level surgery for fixed musculotendinous contractures and bony deformities in older children. This report highlights the utility of BTX in the treatment of cerebral palsy in children. We include techniques for administration, side effects and possible resistance as well as specific use in the upper and lower limbs muscles

Potent new small-molecule inhibitor of botulinum neurotoxin serotype A endopeptidase developed by synthesis-based computer-aided molecular design.

Directory of Open Access Journals (Sweden)

Yuan-Ping Pang

2009-11-01

Full Text Available Botulinum neurotoxin serotype A (BoNTA causes a life-threatening neuroparalytic disease known as botulism. Current treatment for post exposure of BoNTA uses antibodies that are effective in neutralizing the extracellular toxin to prevent further intoxication but generally cannot rescue already intoxicated neurons. Effective small-molecule inhibitors of BoNTA endopeptidase (BoNTAe are desirable because such inhibitors potentially can neutralize the intracellular BoNTA and offer complementary treatment for botulism. Previously we reported a serotype-selective, small-molecule BoNTAe inhibitor with a K(i (app value of 3.8+/-0.8 microM. This inhibitor was developed by lead identification using virtual screening followed by computer-aided optimization of a lead with an IC(50 value of 100 microM. However, it was difficult to further improve the lead from micromolar to even high nanomolar potency due to the unusually large enzyme-substrate interface of BoNTAe. The enzyme-substrate interface area of 4,840 A(2 for BoNTAe is about four times larger than the typical protein-protein interface area of 750-1,500 A(2. Inhibitors must carry several functional groups to block the unusually large interface of BoNTAe, and syntheses of such inhibitors are therefore time-consuming and expensive. Herein we report the development of a serotype-selective, small-molecule, and competitive inhibitor of BoNTAe with a K(i value of 760+/-170 nM using synthesis-based computer-aided molecular design (SBCAMD. This new approach accounts the practicality and efficiency of inhibitor synthesis in addition to binding affinity and selectivity. We also report a three-dimensional model of BoNTAe in complex with the new inhibitor and the dynamics of the complex predicted by multiple molecular dynamics simulations, and discuss further structural optimization to achieve better in vivo efficacy in neutralizing BoNTA than those of our early micromolar leads. This work provides new insight

Alternative Approach to Traumatic Stensen’s Duct Injuries Accompanied by Glandular Involvement: Botulinum Toxin Injection to the Gland in Conjunction with Microsurgical Repair of the Duct in an Acute Setting

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Mert Çalış

2017-12-01

Full Text Available Objective: The aim of this study was to evaluate the long-term results of a simultaneous application of botulinum toxin to the parotid gland in conjunction with the microsurgical repair of the duct in an acute setting and to encourage using botulinum toxin as a first-line option to prevent future complications associated with glandular involvement. Material and Methods: Three patients who were referred to the Plastic Surgery Clinic by the emergency room of the Hacettepe University Hospital after maxillofacial trauma are reviewed in this study. Exploration of the facial nerve and Stensen’s duct was planned for all patients within the first 72 hours after their injuries. After intraoral catheterization of the Stensen’s duct through the papilla using an epidural catheter, microsurgical end-to-end anastomosis was performed. Concurrently, 100 units of botulinum toxin A was injected at standardized eight points to the parotid gland. Results: Postoperative magnetic resonance (MR sialography revealed patency in all patients at the end of postoperative first year. The mean postoperative parotid volume of the injured and non-injured sides were 19.82±10.55 cm3 and 17.79±10.98 cm3, respectively, and the results were found to be comparable. Fibrillation potentials in the postoperative electromyography recordings and clinical examination demonstrated nerve regeneration. Conclusion: Botulinum toxin A appears to be effective in treating duct injuries accompanied by glandular involvement in an acute setting, as well as in preventing long-term complications.

A comparative trial of ice application versus EMLA cream in alleviation of pain during botulinum toxin injections for palmar hyperhidrosis

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Alsantali A

2018-04-01

Full Text Available Adel Alsantali Department of Dermatology, King Fahd Armed Forces Hospital, Jeddah, Saudi Arabia Background: Botulinum toxin is a safe and effective therapy for palmar hyperhidrosis, but the associated pain from injections limits the usefulness of this method of treatment. Purpose: To evaluate the efficacy of Eutectic Mixture of Local Anesthetics (EMLA cream versus ice application in alleviation of pain during botulinum toxin injections for palmar hyperhidrosis. Methods: In this prospective study, 23 patients underwent palm Botox injections to treat their excessive sweating. In each patient, EMLA cream was applied to one palm and ice was applied directly before the injections in the other palm. Pain was evaluated using a Visual Analog Scale. Results: Statistically, there was a significant difference in pain control between EMLA cream group and ice application group (p<0.05. The average pain score on the hands where EMLA cream was applied was 8.9 (SD=0.81, whereas it was 4.8 (±0.9 in the ice group. Conclusion: In this study, the successful use of ice application in reducing pain by 40% in comparison to EMLA cream during Botox toxin injection for palmar hyperhidrosis is demonstrated.Keywords: ice, local anesthetics, EMLA, palmar hyperhidrosis, Botox injection, pain reduction

Crystal structure of the HA3 subcomponent of Clostridium botulinum type C progenitor toxin.

Science.gov (United States)

Nakamura, Toshio; Kotani, Mao; Tonozuka, Takashi; Ide, Azusa; Oguma, Keiji; Nishikawa, Atsushi

2009-01-30

The Clostridium botulinum type C 16S progenitor toxin contains a neurotoxin and several nontoxic components, designated nontoxic nonhemagglutinin (HA), HA1 (HA-33), HA2 (HA-17), HA3a (HA-22-23), and HA3b (HA-53). The HA3b subcomponent seems to play an important role cooperatively with HA1 in the internalization of the toxin by gastrointestinal epithelial cells via binding of these subcomponents to specific oligosaccharides. In this study, we investigated the sugar-binding specificity of the HA3b subcomponent using recombinant protein fused to glutathione S-transferase and determined the three-dimensional structure of the HA3a-HA3b complex based on X-ray crystallography. The crystal structure was determined at a resolution of 2.6 A. HA3b contains three domains, domains I to III, and the structure of domain I resembles HA3a. In crystal packing, three HA3a-HA3b molecules are assembled to form a three-leaved propeller-like structure. The three HA3b domain I and three HA3a alternate, forming a trimer of dimers. In a database search, no proteins with high structural homology to any of the domains (Z score >10) were found. Especially, HA3a and HA3b domain I, mainly composed of beta-sheets, reveal a unique fold. In binding assays, HA3b bound sialic acid with high affinity, but did not bind galactose, N-acetylgalactosamine, or N-acetylglucosamine. The electron density of liganded N-acetylneuraminic acid was determined by crystal soaking. In the sugar-complex structure, the N-acetylneuraminic acid-binding site was located in the cleft formed between domains II and III of HA3b. This report provides the first determination of the three-dimensional structure of the HA3a-HA3b complex and its sialic acid binding site. Our results will provide useful information for elucidating the mechanism of assembly of the C16S toxin and for understanding the interactions with oligosaccharides on epithelial cells and internalization of the botulinum toxin complex.

Kinematic aiming task: measuring functional changes in hand and arm movements after botulinum toxin-A injections in children with spastic hemiplegia.

NARCIS (Netherlands)

Rameckers, E.A.A.; Speth, L.A.; Duysens, J.E.J.; Vles, J.S.; Smits-Engelsman, B.C.M.

2007-01-01

OBJECTIVE: To describe different aspects of a kinematic aiming task (KAT) as a quantitative way to assess changes in arm movements within 2 wks after botulinum toxin-A (BTX-A) injections in children with spastic hemiplegia. DESIGN: Intervention study randomized clinical trial; follow-up within 4 wks

Botulinum Toxin Type A as a Therapeutic Agent against Headache and Related Disorders

Directory of Open Access Journals (Sweden)

Siro Luvisetto

2015-09-01

Full Text Available Botulinum neurotoxin A (BoNT/A is a toxin produced by the naturally-occurring Clostridium botulinum that causes botulism. The potential of BoNT/A as a useful medical intervention was discovered by scientists developing a vaccine to protect against botulism. They found that, when injected into a muscle, BoNT/A causes a flaccid paralysis. Following this discovery, BoNT/A has been used for many years in the treatment of conditions of pathological muscle hyperactivity, like dystonias and spasticities. In parallel, the toxin has become a “glamour” drug due to its power to ward off facial wrinkles, particularly frontal, due to the activity of the mimic muscles. After the discovery that the drug also appeared to have a preventive effect on headache, scientists spent many efforts to study the potentially-therapeutic action of BoNT/A against pain. BoNT/A is effective at reducing pain in a number of disease states, including cervical dystonia, neuropathic pain, lower back pain, spasticity, myofascial pain and bladder pain. In 2010, regulatory approval for the treatment of chronic migraine with BoNT/A was given, notwithstanding the fact that the mechanism of action is still not completely elucidated. In the present review, we summarize experimental evidence that may help to clarify the mechanisms of action of BoNT/A in relation to the alleviation of headache pain, with particular emphasis on preclinical studies, both in animals and humans. Moreover, we summarize the latest clinical trials that show evidence on headache conditions that may obtain benefits from therapy with BoNT/A.

Physical therapies as an adjunct to Botulinum toxin-A injection of the upper or lower limb in adults following neurological impairment

Directory of Open Access Journals (Sweden)

Kinnear Bianca Z

2012-06-01

Full Text Available Abstract Background Spasticity of muscles is a common consequence of central nervous system impairment. Traditionally, neurological rehabilitation for spasticity has involved occupational and physical therapy; however, increasingly Botulinum toxin–A injections may be provided. Injection effects are temporary. Consequently, understanding the effect of adjunct physical therapies will help inform multimodal rehabilitation decisions. Presently, these effects are not known. This systematic review will identify and summarize evidence on physical therapies used after Botulinum toxin-A injection to improve motor function in adults with neurological impairments. Method Systematic searching of seven electronic databases will occur to identify relevant randomized trials. Available trial data will be extracted into a list of pre-defined primary outcomes, including range of movement, spasticity and functional limb use. Pre-defined secondary outcomes will also be reviewed where trials have these data available for reporting. Effects will be expressed as mean differences or standardized mean differences with 95% confidence intervals (CI. Where possible, comparable results will be meta-analyzed, and a summary of the available pool of evidence produced. All randomized controlled trials will be rated using the PEDro methodological quality scale. Where possible, study data will be meta-analyzed using RevMan 5 Software. The protocol was registered in PROSPERO international prosepective register of systematic reviews (PROSPERO 2011:CRD42011001491. Discussion Review results will be the most comprehensive answer available to the following question: Are physical therapies clinically effective after Botulinum toxin-A injections in adults with neurological spasticity? Results will inform healthcare providers and managers who determine who gets access to and provision of Botulinum toxin-A injection and whether this is done with or without physical therapies. Results

Toxin production by Clostridium Botulinum type B (proteolitic) in radurized raw fish

International Nuclear Information System (INIS)

Suhadi, F.

1978-01-01

The earliest toxin production by three proteolytic strains of Cl. botulinum type B was determined in irradiated and unirradiated raw fish (Rastrelliger sp., Euthynnus sp., and Scomberomorus sp.) under the storage temperatures of 20, 10, and 5degC. The estimation of maximum storage life was evaluated by an untrained panel on uninoculated fish samples and in parellel the total bacterial counts were also determined. Percentage data of the toxic samples were analyzed according to a fully randomized design involving factorial treatments. In unirradiated samples with inoculum levels of 10 2 -10 6 spores per gram and stored at 20degC, the earliest toxin production was detected after the samples were spoiled. While in irradiated samples toxin were detected before the end of the storage life or after the samples were spoiled, depending on the levels of inoculum. In general, both in unirradiated and irradiated samples inoculated with 10 2 -10 6 spores per gram and stored at 10degC, the earlieast toxin production was detected after the samples were spoiled. While the samples were stored at 5degC, no toxic samples were found up to 30 days of storage when the experiment were terminated. The percentage of toxic samples was shown highly effected by type B strains, fish species, inoculum levels and storage time, when the storage temperature is 20degC. But no significant difference was found after treatment with irradiation doses. In general the interaction effects between those treatments on the percentage of toxic samples showed no significant difference. (author)

Botox® after Botox® - a new approach to treat diplopia secondary to cosmetic botulinic toxin use: case reports

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Cassiano Rodrigues Isaac

2012-06-01

Full Text Available A new technique for the treatment of diplopia secondary to cosmetic botulinum toxin A use is described. In this interventional case reports, two consecutive patients who developed diplopia after periocular cosmetic use of botulinum toxin A were treated with intramuscular botulinum toxin A injection into the antagonist extraocular muscle. Diplopia resolved in both patients in less than 1 week with no side effects or complications. In conclusion, the injection of intramuscular botulinum toxin A is an encouraging option for treatment of diplopia secondary to botulinum toxin A use for facial lifting.

Progress on Botulinum Toxin Type A-Induced Pain Relief in the Field of Plastics.

Science.gov (United States)

Lu, Xiaona; Chen, Guocheng; Ren, Pengjie; Yang, Yan; Fan, Fei

2017-11-01

To retrospectively evaluate the effectiveness of Botulinum Toxin Type A (BTX-A) injections relieve pain in the field of plastic surgery and postoperative rehabilitation, and discuss the analgesic mechanism of BTX- A in plastics and related research progress. From appearance to September 1, 2016, PUBMED, EMBASE, and Web of Science were searched, using the key words related to "Botulinum Toxin Type A" and "Pain." Furtherly, nonplastic surgery-related literature was excluded by manual screening. Eleven literatures met the inclusion criteria, including 6 prospective controlled cohorts, 4 patient series, and 1 retrospective cohort. These studies involved Lower Limb, Breast, Hallux, Amputees, and Temporomandibular joint disk disfigurement and enrolled 402 patients. Among the patients, 360 received intraoperative BTX-A injection at the time of the main surgical procedure, 16 injected postoperatively and 26 did not undergo surgery. And 85.32% reported pain alleviation and 69.96% got favorable side effects and no one occurred major adverse effects. But 1.83% accepted injections more than once. Mechanism analysis explained these studies' results and demonstrated the analgesic effectiveness of BTX-A in plastics with nociceptive pain, inflammatory pain, and neuropathic pain. The results suggest that BTX-A may induce postoperative pain associated with plastic surgeries relief. But the available data of outcome assessment involved in this review are inconsistent and failed to meet methodological rigor. And pain alleviations are influenced by many factors. So further randomized controlled clinical trials with large sample sizes are needed to support this practice, determine standard usage methods, and establish corresponding specification systems.

Isosorbide dinitrate ointment vs botulinum toxin A (Dysport®) as the primary treatment for chronic anal fissure: a randomized multicentre study

NARCIS (Netherlands)

Berkel, A.E.M.; Rosman, C.; Koop, R.; van Duijvendijk, P.; van der Palen, Jacobus Adrianus Maria; Klaase, J.M.

2014-01-01

Aim Nitric oxide donors, such as isosorbide dinitrate ointment (ISDN), are considered as first-choice agents in the treatment of chronic anal fissure. Injection with botulinum toxin A in the internal anal sphincter is often used as a second-line therapy, although it may give better results and fewer

Is Botulinum Toxin Type A a Valuable Adjunct During Femoral Lengthening? A Randomized Trial.

Science.gov (United States)

Park, Hoon; Shin, Soowan; Shin, Han Sol; Kim, Hyun Woo; Kim, Dong Wook; Lee, Dong Hoon

2016-12-01

Reduced joint ROM and distraction-induced pain are common complaints of patients who have undergone gradual femoral lengthening. Attempts to reduce the effects of lengthening on joint motion have included the use of botulinum toxin to reduce the muscle forces that restrict motion. The benefits of this approach during femoral lengthening, however, have not been conclusively established. We wished to evaluate the effects of botulinum toxin type A (BtX-A) injection in the anterior thigh muscles during femoral distraction osteogenesis on adjacent joint ROM and distraction-induced pain. We asked: (1) Does injection of BtX-A in the quadriceps muscles lead to improved knee and hip motion during femoral lengthening? (2) Does injection of BtX-A reduce pain during femoral lengthening? A single-center, double-blind, randomized placebo-controlled trial was conducted. Forty-four patients (88 femurs) undergoing bilateral femoral lengthening for familial short stature were included in the study. BtX-A (200 IU) was injected intraoperatively in the quadriceps muscles of one thigh. An equal volume of sterile normal saline was injected in the other thigh as a control. Selection of the limb receiving the toxin was randomized. Clinical evaluation included a VAS score for pain measurement, ROM evaluation of the hips and knees, and measurement of thigh circumference. Side-to-side differences were analyzed throughout the entire consolidation phase. No patients were lost to followup, leaving 44 patients (88 femurs). The mean followup was 26 months (range, 14-40 months). The distraction rate and final length of gain were similar between treated and control limbs. A priori power analysis suggested that 44 legs were required in each group to achieve statistical significance of 0.05 with 90% power to detect a 50% difference in treatment effect between treatment and control groups. There were no differences in hip ROM, knee ROM, or maximal thigh circumference between the two lower extremities